July 2009 Archives

By Mary Brolley, Staff Writer

acciberries.jpgAcai berries come from the acai palm tree (Euterpe oleracea) found in Central and South America. The acai berry has been used by native Central and South Americans for centuries -- it makes up 42% of the region's total food intake. 

A relative of the blueberry and cranberry, the acai berry has become popular in the United States because it's believed to have tremendous health benefits. It's touted as the latest "super fruit" due to high antioxidant levels. An antioxidant is a substance that protects the body's cells from damage caused by unstable molecules known as free radicals.

Acai berries contain anthocyanins and flavonoids, both powerful antioxidants that protect the body from environmental stressors (noise, pollution, traffic) and reduce the effects of free radicals. By reducing the effects of free radicals, these antioxidants help lower the risk of heart disease and cancer, reduce inflammation and possibly slow the spread of cancer cells.

A study conducted by the Arkansas Children's Nutrition Center found that the antioxidant capacity of freeze-dried acai berries have the highest antioxidant activity of any food reported to date. A separate study conducted at the University of Florida showed that extracts from acai berries generated a self-destruct response in up to 86% of leukemia cells tested. A similar study conducted at Texas A&M University found that 12 to 24 hours after consumption of acai pulp and applesauce, antioxidant activity in the blood increased significantly. This means that acai consumption can stimulate the body's antioxidant level and its protective effects from cancer, heart disease and possibly other illnesses.

When eaten as a food, acai berry appears to be safe. However, since it hasn't been sufficiently researched, side effects and dosing of the supplement form have not been determined.

The acai berry is sold in supplement form in various health food stores and supermarkets in the United States. It also can be found as an ingredient in some juices, drinks, liquors, jellies, applesauce and ice cream. The supplements cost about $7 for 60 capsules and the food items range from $4 to $15. More cost-effective antioxidants include blueberries and cranberries, which can be purchased at your local grocery store as juice or a food item for as little as $1.50.

By: Laurence Cooper, M.D., Ph.D., associate professor, Department of Pediatrics

Significant advances have been made in the treatment of pediatric cancer through clinical trials that compare chemotherapy regimens in patients to determine which one works best against a particular cancer. While this strategy has worked for the past three decades to improve the chances of children surviving cancer to 80%, this approach is reaching a point of diminishing returns.

Why is this?
For one, pediatric oncologists rely on chemotherapy drugs that were mostly developed decades ago. For children whose cancer relapses, their options are limited due to the lack of new agents on the market. In addition, relapsed cancers tend to be resistant to chemotherapy.

Secondly, for childhood cancer survivors, the drugs that have cured them also have made a long-term impact on their bodies. According to the Childhood Cancer Survivor Study, nearly 75% of childhood cancer survivors will develop chronic health problems or secondary cancers within 30 years of diagnosis. If a child is diagnosed between the ages of 5 and 10, that means that 35- to 45-year-olds are having major problems. New agents are needed to improve the chances of surviving and reduce the toxicities of treatment.

What are the barriers?
The problem pediatric oncologists face is a lack of new drugs designed for pediatric cancers. The bottom line for biopharmaceutical companies is that they typically cannot recoup the financial cost of developing new therapies for rare cancers, such as those in children. So, pediatric oncologists often rely on medicines that were developed for adults and then project their impact for children. This "hand-me-down" approach has inherent problems as no cancer therapy for adults is invented anticipating greater than a 30-year survival from disease.

What's the solution?
Cell-based therapies can provide an answer to these barriers. Many people think of cell therapy as simply bone marrow transplants, but the world of cell therapy encompasses even more therapeutic approaches to treating cancer.

Cell therapy is an approach being pioneered at a few centers to harness the power of a child's immune system to target their tumor. These therapies can be made specifically to kill cancer cells based on an entirely different principal than disrupting cell division like chemotherapy does. You and I are born with an immune system that has an exquisite ability to separate invading organisms from our own cells. Thus, for most of us, we can fight off an infection without fighting off ourselves.

Investigators at M. D. Anderson and elsewhere have developed tools to turn immune cells into cancer-fighting cells. Clinical trials within the Children's Cancer Hospital at M. D. Anderson are now establishing the safety and feasibility of this approach. Investigators are infusing two types of immune cells, T cells and NK cells, as an approach to safely attacking tumors that are resistant to chemotherapy. Just as your naturally occurring immune cells provide ongoing surveillance against recurrence of infection, so the expectation is that these cancer-specific immune cells, provided through immunotherapy (a type of cell therapy), will patrol the child's body and be able to respond and possibly prevent recurrence.

We live at the beginning of the golden age of cell therapy. Clinical trials are investigating the promise of this approach.

Acupuncture.jpgBy: M. Kay Garcia, DrPH, MSN, RN, LAc, Advanced Practice Nurse, Integrative Medicine Program*

It's important to have realistic expectations about acupuncture. People either don't expect it to work at all, or they expect it to be a "magic bullet" and completely resolve all their health problems. Acupuncture isn't a "magic bullet" and certainly doesn't work for everyone. Most people do get some benefit. Some get a lot of benefit with only a few treatments, while others get a little benefit even after multiple treatments.

The effects of acupuncture also tend to be cumulative, so it's important not to expect too much too soon. At M. D. Anderson, we consider 8-10 treatments as one course, and for long-term problems, multiple courses may be necessary. I often tell patients with chronic conditions, "It's like fertilizing your garden -- don't expect the flowers to bloom tomorrow. In the long-term, though, you should end up with a better result."  

What should I use acupuncture for?
Acupuncture has been shown to be effective for nausea/vomiting and some types of pain. There also is a growing body of evidence for xerostomia (dry mouth) and hot flashes. Although it may  help for other symptoms such as constipation, loss of appetite, fatigue, insomnia, anxiety, depression, peripheral neuropathy and delayed wound healing, not enough rigorous clinical trials have been conducted to draw meaningful conclusions. That being said, as a safe, inexpensive treatment, there's no reason not to try it if you're interested.

So in a nutshell, it's always a good idea to recommend acupuncture when the patient is:

    * Experiencing uncontrolled nausea, vomiting or pain.
    * Experiencing side effects from treatment or medications.
    * Has failed conventional treatment for symptom control.

As a clinician, I often see a synergistic effect when acupuncture is added to a patient's treatment plan. For example, adding it to a comprehensive pain management regimen often allows patients to reduce the amount of medications they're taking and thereby reduce unpleasant or debilitating side effects. Dr. Moshe Frenkel, medical director of our Integrative Medicine Program, always says, "Can't hurt, might help, why not!"

Is it safe?
Acupuncture has been shown to be extremely safe when given by a qualified and licensed acupuncturist. Risks include fainting, mild discomfort, bruising and possible infection. As for the latter two, because these are tiny, solid stainless steel needles, the risk of either bleeding or infection is lower with acupuncture than with venipuncture. Even for patients taking low molecular weight heparins, aspirin or NSAIDS, the risk of excess bleeding with acupuncture is very low.

Why does acupuncture research often show mixed results?
I think there are many reasons. Sometimes it's because of poor study design. Sometimes researchers ask the wrong questions, and sometimes it's because we don't have a clear understanding of how acupuncture works. Recent data from Germany show that although acupuncture points are indeed areas on the skin with reduced bioelectric resistance, this characteristic varies over time; thus, timing of the treatment may be key to its effectiveness. To date, very little research has evaluated this aspect of acupuncture, even though it's an important concept in traditional Chinese medicine theory.

Putative mechanisms of acupuncture are multiple, and although there's certainly a large placebo effect, fMRI and animal studies clearly indicate there's a physiologic response above and beyond placebo. Let's face it, if it works on lab rats, there's something more than the "power of suggestion" at work. In terms of pain, for example, animal studies have shown the effects of acupuncture are reversed with Naloxone, a powerful opioid antagonist. For other symptoms such as xerostomia, mechanisms are a little harder to explain, but studies are under way to explore these questions.

Needless to say, we still have a lot to learn about the mechanisms and efficacy of acupuncture. However, a growing body of evidence indicates that it can be an important adjunct in the care and treatment of cancer patients

NCI on acupuncture
American Cancer Society on acupuncture
Place of ... wellness at M. D. Anderson

* Byline correction made on 08/11/09

The mission of M. D. Anderson's Odyssey Program is to support the best among the newest generation of cancer researchers here and encourage them to explore novel areas of clinical, translational, basic or population-based cancer research. To fulfill this mission, the Odyssey Program supports them and their research during their post-doctoral training, a critical career phase during which scientists first develop independence and a funding track record.

Odyssey Fellowships are given annually, with a start date of Sept. 1, following an open call for applicants and a rigorous peer-review process. This round we had 41 applications from 26 departments and were able to support three new fellows, about 7%, making the Odyssey Program's competition one of the toughest. You can compare this to the National Institutes of Health payline, which even in the toughest times has stayed above 10%.

The three awardees who will join the Odyssey Program in 2009 are:

• Dr. Calley Hirsch from Dr. Sharon Dent's lab (Department of Genetics): "The Role of Gcn5 in Mouse Embryonic Stem Cells"

• Dr. Marites Melancon from Dr. Jason Stafford's lab (Department of Imaging Physics): "Targeted Nanoshell-Based Agents for MRI-Guided Thermal Ablation of Head and Neck Cancer"

• Dr. Sofie Claerhout from Dr. Gordon Mills' lab (Department of Systems Biology): "Tumor Dormancy and Autophagy -- Implications for Breast Cancer"

I want to thank the Odyssey Program Advisory Committee for their hard work in scoring these applications.

The Odyssey Program is supported by  endowments from the Theodore N. Law Award For Scientific Achievement, Houston Endowment, Inc. Award for Scientific Achievement, H-E-B Award for Scientific Achievement, Kimberly-Clark Foundation Award for Scientific Achievement, Cockrell Foundation Award for Scientific Achievement, The Kimberly Clark Fund for New and Innovative Research. Recently the program has received generous support from the CFP Foundation and the Arnold Family Foundation.

Cancer survivors know that the effects of the disease and its treatments aren't merely physical. While each person is unique, many cancer survivors share some common concerns.

One of the most basic is the fear that the cancer will recur. It's important to remember that while you can't control whether cancer recurs, you can control how much you let the fear of recurrence impact your life.

A first step in coping with fear is to try not to feel guilty or ignore feelings in hopes that they'll go away. Instead, there are certain things you can do to help cope with this fear:

• Talking often reduces fears and anxieties. Talk with your health care team or friends, or join a support group.

• Try writing down your thoughts and feelings in a journal.

• Try other complementary modalities like yoga, music therapy, tai chi, guided imagery, reflexology and massage. There are reputable centers all across the country that offer classes in these disciplines.

M. D. Anderson Resources

M. D. Anderson's Place ... of wellness provides a service where persons touched by cancer may enhance their quality of life through programs that focus on the mind, body and spirit. It offers more than 75 complementary therapy programs, most are free of charge.

Place ... of wellness is open to anyone touched by cancer, their family members and caregivers, whether or not they were treated at M. D. Anderson. No physician referral is required. For more information, call 713-794-4700

Other Resources
Yoga Bear Blog 
Integrative Therapies at Dana Farber
Integrative Therapy Classes at Sloan Kettering
Integrative Services at Cleveland Clinic

fisch_signingFor some reason, I have a track record for working in areas of cancer medicine that are fundamentally patient-centered, difficult to understand based on their labels and challenging to briefly explain. Three examples: palliative care, general oncology and integrative medicine. What do these topic areas mean to you? 

I arrived at M. D. Anderson in November 1999. I had been trained in internal medicine and hematology/oncology, and had spent the first two years of my career as an academic oncologist focusing on the care of genitourinary malignancies. But I had decided to pursue my interests in issues related to symptom management and quality of life, so my job position here was in the Department of Palliative Care and Rehabilitation.

The department was new, and I would be asked by faculty and staff on a frequent basis, "what is palliative care, anyway?" I would babble something about quality of life and helping people live better, but I couldn't explain it coherently before the questioning colleague got off the elevator or veered in a different direction. So I decided to find a succinct definition that I liked, and rehearse and memorize a version of it. Here's what I memorized:

"Palliative care is comprehensive, interdisciplinary care for patients with life-limiting illness, where the focus of care is enhancing quality of life and reducing suffering for the patient and family."

OK, so what's general oncology? It's the ultimate paradox at our institution, which is well known for incredible subspecialty expertise in so many areas. Why would M. D. Anderson want "general oncology?"

On our main campus, general oncologists have a role in the initial evaluation of complex international patients as they're evaluated and cared for in preparation for the appropriate subspecialty, multidisciplinary team. Moreover, they're often called upon to help navigate complex care when multiple specialty teams are involved. General oncologists provide care in our Integrative Medicine Clinic as well.

Our Department of General Oncology leads the medical oncology care at Lyndon B. Johnson General Hospital and at our community-based clinical care centers. Also, general oncologists often lead and participate in patient-oriented research projects and clinical trials that address issues cutting across different diseases, and collaborate on other projects and clinical trials that are led by subspecialists.

Finally, if general oncologists evaluate patients in the Integrative Medicine Clinic, what exactly is integrative medicine? According to the Consortium of Academic Centers in Integrative Medicine, it's "the practice of medicine that reaffirms the importance of the relationship between practitioner and patient, focuses on the whole person, is informed by evidence, and makes use of all appropriate therapeutic approaches, health care professionals and disciplines to achieve optimal health and healing."

To me, that sounds exactly like good medical care -- just the kind of patient-centered care that people expect. The thrust of the care in integrative medicine is tailoring to each individual patient a program that improves his or her health and well-being, above and beyond the disease-focused expert care provided by other care teams.

Elizabeth Travis 1As the associate vice president for women faculty programs, still a relatively new program at M. D. Anderson, I am often asked "What do you do?" and "Why do we need this office?"   
When I think about these questions, it comes down to three issues

We need all the best minds to focus on finding cures and treating cancer.
The frequently quoted figure is that the pipeline for physicians and scientists contains 50% women. This has been true for the last five years, but these numbers aren't reflected in faculty ranks at any institution. More relevant to M. D. Anderson, however, is that 49% of the fellows completing oncologic fellowships are women -- although this percentage is specialty dependent -- but only 24% of practicing oncologists are women. That begs the question, "What happens to these women?"

For the Ph.D.s, we know that the pipeline from assistant professor to professor is leaky. So, by the time we reach the professor rank, the numbers of women have greatly diminished to only 20%. With the impending shortage of oncologists and the projected increase in cancer incidence in our aging population, compounded by the good news of increased numbers of survivors, M. D. Anderson must cultivate and fully engage women scientists and physicians if we are to fulfill our mission of Making Cancer History.

Women Faculty Programs' charge is to initiate and implement initiatives to do just that: recruit, promote and retain women faculty. We work across the board to examine existing policies and recommend revisions, so that they're more aligned with women's (and frequently men's) lives. Examples are extending the tenure/tenure track clock for faculty who have a new child in the family and implementing career development programs. By the way, many of these policies "lift all boats" as they're gender neutral policies.

We also help identify and recruit women to leadership positions in the institution, since it's clear that more women at the top attract more women at all levels of the organization. In addition, our patients tell us that they want doctors who are like them -- men and women, and from a variety of cultures.

Finally, it's good business. Research indicates that organizations with the highest   representation of women on their boards outperform those with the least by 53%. In terms of sales, companies with more women board directors outpace those with fewer by 42%. So, too, with medicine and science. Who could argue with that?

The other physician-scientist problem: Where have all the young girls gone? (Nature)

A gender gap in the next generation of physician-scientists: medical student interest and participation in research (PubMed)

Legends and Legacies: Personal Journeys of Women Physicians and Scientists at M. D. Anderson Cancer Center

By: Dean A. Lee, M.D., Ph.D.assistant professor, Department of Pediatrics, Cell Therapy Section

Why all the fuss?
You can hardly be alive and breathing and not be aware of the ethical and political struggles the world has endured over stem cells for the past several years. In a world that's already jaded to the exposure the media gives to new advances in medical science, stem cell research has become the poster child for what the hyperbole of Washington and Hollywood can do to (for?) science. 

Last week, the Washington Post reported the release of new federal rules governing which embryonic stem cells could be used for research, and the week prior U.S. News & World Report ran an article discussing the promise of stem cells. Three weeks ago, My Sister's Keeper was released in theaters, a cinematic adaptation of Jodi Picoult's best-selling novel about the potential legal and ethical conflicts of stem cell donors.

In spite of all the recent discussion on this subject, there's still much confusion about the different kinds of stem cells, the procedures available, and the issues surrounding stem cell therapies.
What is a stem cell?
The great majority of cells in our body have one very specialized function: they make hair, or sweat, or they twitch, or they make insulin, or they absorb nutrients, etc. They dutifully perform these tasks until they die. Somewhere in nearly every organ, though, is a cell that makes replacements for these cells that die, and occasionally, also makes a replacement for itself. Something like a beehive, where almost all of the bees on the colony are specialized as drones or workers, but somewhere deep in the hive is a queen making more of them. And, every so often, the queen is able to make another queen. That ability to reproduce itself is the hallmark of a stem cell.

Forward motion
Cells in our body generally become more and more specialized until they become fully functional mature cells. This is a process called differentiation, and this process typically moves in only one direction. That is, once a cell has gained a specific function, it usually can't go back to being a less-specialized cell. This is why embryonic stem cells are usually described as having so much potential -- because they can, under the right circumstances, become anything. They are, coming from an embryo, the least specialized human cell that there is.

The embryonic stem cell eventually gives rise to more specialized stem cells: skin stem cells, liver stem cells, blood vessel stem cells, or blood-forming stem cells (referred to as hematopoietic stem cells or HSC). These cells can't make any cell in the body, but can make many different cells of a particular tissue type. So, the answer to the question in the title of this blog is "no." There are many regulations regarding HSC, but none of them are affected by the regulations for embryonic stem cells.

Hematopoietic stem cellsImage from NIH Stem Cell Information

Hematopoietic stem cells
If all you need is blood-forming stem cells, however, the medical research community has a wide variety of well-established sources and procedures -- many that have been in use for more than 30 years. We can obtain these cells from their native source (bone marrow), from the blood of a donor or from a discarded umbilical cord. All of these sources are rich in HSCs and none of them come from an embryo. 

Researchers at M. D. Anderson are investigating ways to grow more cells from cord blood, purify the stem cells from blood, increase the number of stem cells in the blood, change the genes of stem cells, grow special immune cells from stem cells and make the stem cells better at finding their way back to the bone marrow. In addition, we have exciting new research using a new kind of stem cell from the structural part (instead of the blood-forming part) of the bone marrow, called mesenchymal stem cells. Some of these new approaches are already available to patients in clinical trials.

According to the 2009 "Best Hospitals" survey published by U.S. News & World Report
M. D. Cancer Center is the leading hospital in the nation for cancer care.

U.S. News ranks hospitals in 16 specialties, from cancer and heart disease to respiratory disorders.  A total of 4,861hospitals are reviewed, and only 174 hospitals score high enough to be ranked in even one of the 16 specialties.

In addition to the top ranking for cancer, we earned the most subspecialty rankings we have ever gotten, with top listings in ear, nose and throat (2), urology (9), gynecology (12), digestive disorders (23) and diabetes and endocrine disorders (41).

"This national ranking is a great point of pride among our employees and volunteers, one that we share with our patients, survivors and their families," said John Mendelsohn M.D., president of M. D. Anderson. "This year, with the national economic downturn and the impact of Hurricane Ike, the news is especially welcome as we redirect and recommit our resources to the many needs of those we serve."

How do you discuss a topic that most people hope they never have to think about, and that is about as appealing as a fuzzy brown Chinese gooseberry or a bug-eyed Patagonian toothfish? Like the wildly successful re-marketing of the popular Kiwi fruit (formerly Chinese gooseberry) and the Chilean sea bass (formerly Patagonian toothfish), the key to talking about cancer clinical trials is framing the issue in ways that are relevant and meaningful to the audience.  
gooseberry_fish.jpgIn Texas, 70% of cancer patients are white, even though the white population makes up only 48% of the population of Texas. Hispanics make up 37% of the population, but only 17% of new cancer cases. This surprising statistic is largely due to the fact that while minorities experience higher cancer rates in general, there are fewer minorities currently diagnosed with cancer. Minorities as a group -- in particular Hispanics -- are younger than the white population, and age is a significant risk factor for cancer. The older you are, the more your risk for cancer increases. In Texas, 70% of people older than 70 are white.
To reach healthier, younger people -- in particular Asians and Latinos -- we talk about cancer preparedness as a tool to maintain and protect their health and that of their families.

Residents of the Texas Gulf Coast are very familiar with the concept of hurricane preparedness. Every hurricane season, meteorologists are the most visible people on TV, as they share the latest news about potential hurricanes forming, and communicate messages of awareness, preparation and appropriate action. The annual rituals of stocking batteries and canned foods, filling the tub with water and the tank with gas become matter-of-fact behaviors, and not reasons for fear or distress. Certainly we hope that the hurricane does not head our way, but if it does, we will know what to do and how to do it.

Cancer preparedness takes the same approach. Health education specialists in the Minority & Women Clinical Trials Recruitment Program promote cancer awareness, prevention and screening with Hispanic and Asian audiences. They provide information about treatment options, including clinical trials, as resources that audiences can use to help themselves, their parents and elders decide the most appropriate course of action, for optimal survival and outcome, should the hurricane of cancer enter their lives. 

In 2007, I was diagnosed with prostate cancer. After radical prostatectomy surgery, radiation and two years of hormone therapy, I have learned that "attitude matters."

My mother died of colon cancer when I was just entering college. What I best remember of her 15-year fight was her attitude. When family and friends were trying to pull themselves together after each surgery, my mother was always trying to get back to work, back to her garden, back to living. My dad had a rich life and, at age 78, died of prostate cancer. On his last day, he walked around the block carrying his oxygen bottle and stopped to listen to the cardinals sing.

As a wellness coach I've worked hard to take care of my body, but my cancer journey has taught me that a body disconnected from the mind-spirit connection can easily get lost. One of my favorite body-mind-spirit authors, Brian Luke Seward, has written many books and articles about stress management, resilience, meditation and attitude. In his book "Stand Like Mountain, Flow Like Water" he suggests that our "attitudes are the paintbrush with which we color the world."  

What paintbrush have you colored your world with today? Some days our self-talk can become so negative or fear-based that our thoughts become what I call "stinking thinking" or "toxic thoughts." This negative thinking not only affects the way we feel, but also how we act and treat ourselves and others.  

How do you stop stinking thinking? The experts say there are several things we can do to shift to a positive mind-set. The one I like the most is GRATITUDE. One of my favorite little books on gratitude is M.J. Ryan's "Attitude of Gratitude." It's 180 pages packed full of stories and affirmations. Remember that gratitude is like a flashlight, lighting up what's already there and then we no longer take it for granted.

FishtanksTry this. Next time you walk around M. D. Anderson, take a look at how the physical environment has been set up to have a positive effect on attitudes. I bet, like me, you have a favorite painting? I love the canyon series that hangs in our Cancer Prevention Building. Then there are the panels in the hallways that tell the stories of patients' cancer journeys and employees' dedication to our mission. Those always inspire me. I also really love the fish tanks, as they provide an instant getaway. They are so big that I often imagine I am scuba diving, which instantly turns my attitude.  

The Place of ... wellness also provides many classes and creative opportunities for patients and families that positively affect attitude.  

As a cancer survivor and wellness coach, my life experience has taught me that attitude is a big part of my cancer journey and how I greet, meet and grow each day. This is a journey we all share with so many others, and M. D. Anderson has an attitude about fighting cancer.

Fighting cancer takes more than good diagnoses and the best treatments. It also takes a staff with an attitude of being the best at what they do and creating an environment in which patients are not just empowered, but are given a cancer-fighting attitude that they share with others as they walk their cancer journeys.

Cancer and Attitude (American Cancer Society)
The Right Attitude for Fighting Breast Cancer (Yahoo Health)

AnasYounes_JulyEvery July, the new academic year begins for U.S. medical training programs. It's a time when new interns and fellows join new hospitals to learn and to be educated.

In addition to taking care of new patients on their first day of service, they have to adapt to a new environment, know the nurses and doctors, find their way in new buildings and, sometimes, new cities, and take care of their own personal and family matters: the rent, car insurance, schools for their kids and finding new friends. I remember the first day of my July internship very well. When you're a doctor, it's a day that you never forget.

It was 1986. I had just moved to New York City three days before and was still trying to settle in. I found a studio apartment overlooking the Statue of Liberty and New York bay, bought new furniture and kitchenware, insured my car, got my phone and electricity connected, and got my clothes and medical books out of the boxes. Then came July 1st.

On my first day, I was very excited but nervous. The graduating intern introduced me to my newly assigned patients with a big smirk on his face that made me even more nervous. I bet that also made some of the patients nervous. 

I sat down for hours reading medical records, reviewing lab and imaging results, current medications and treatment plans. It turned out I also was on call that very first night. I remember having four admissions that night: uncontrolled diabetes with ketoacidosis, uncontrolled congestive heart failure with pulmonary edema, prostate cancer with metastasis, and a patient with HIV and pneumonia. I don't remember other medical details; after all, this was 23 years ago. But I remember everything else very well.

I remember that I was working very hard trying to catch up with my numerous responsibilities, so I didn't have time to eat dinner. But I also remember that my resident noticed and ordered Chinese food for both of us at midnight, which was -- to my pleasant surprise -- delivered to the floor.

I remember that I was getting tired and sleepy by 3:00 a.m. But I also remember that my resident was still awake watching me from a distance, making sure that I was doing all right and offering help. To this day, I remember him falling asleep on a chair behind a desk at 5:00 in the morning after spending the night with me explaining, helping and teaching me new things. We did blood cultures together, looked at blood smears, performed sputum gram stain, looked at chest X-rays, wrote progress notes, and ordered new medicine and laboratory tests. His kindness and generosity not only made me a better doctor, but also reassured patients and ensured their safety. I don't know how I could have survived that night without him.

Thanks to my resident from 23 years ago, I always ask to be assigned to the inpatient service in July. I know many of us like to work with more experienced and knowledgeable fellows while on service; a good fellow can make the life of an attending much easier. But, as odd as it may sound, I always look forward to welcoming and working with the new fellows in July.

So, if I'm not returning your phone calls or e-mails quickly these days, I'm not ignoring you. It's July, and I'm very busy on the inpatient service.

Learn more about medical education at M. D. Anderson

Summer at GSBS

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In a weak moment, I decided to join the 21st century and "blog" on issues for graduate students and advisors.  Summer is one of the most exciting and busy times for both.  For students having chosen a laboratory in which to pursue their degree, this is usually the first time to spend "full time" in the laboratory.  Those fancy experiments you read about in class- now you actually get to do them!  ... 24hrs a day!  If one is to find joy as a research scientist, surely it is in the thrill of seeing the result of a well-designed experiment for the first time, and possibly the first time anyone has seen such a result.  The senior student's notebook so chock full of data and notes looks less and less intimidating as you begin to develop data of your own.   

We advisors actually visit the lab more often, reacquainting ourselves with what a microscope actually looks like, and often musing about the "good ole days" when we did all of our experiments ourselves.  Far be it for me to put a damper on this excitement, but wizened professors never miss an opportunity to offer advice. 

So...summer often provides the best chances to think beyond the next experiment.  Meaning-read of course.  What professor does not advise you to be current with the literature?  But thinking and breathing deeply are even more advisable.  When you get that sought-after result, what is its context?  Does it move you toward a publication or does it move you toward a discovery? -Not always the same. Yet, thinking about where your data lead means thinking about where your career will lead you.  And advisors?  They (on rare occasion) have the time to think as well, and like nothing better than being interrupted from writing the latest modification to the latest animal protocol by students with new data, new ideas and even new problems.  Summer is an excellent opportunity to take advantage of the successful and failed experiments that led to all that gray hair.  So work hard, focus on the next experiment but gaze into the distance. And the balance?

 Kipling had it about right:  

"If you can dream, and not make dreams your master
If you can think, and not make thoughts your aim..."

And those who might be reading this contemplating graduate school?  Summer is the time to think about where.  And, of course, I'd encourage you to think about us, part of the Graduate School of Biomedical Sciences (GSBS). 

Find all the information you might want at:  And information not there?  Hopefully that will become the subject of future blogs.

Common genetic variations spread across five genes raise a person's risk of developing the most frequent type of brain tumor, an international research team reports online in Nature Genetics.

"This is a ground-breaking study because it's the first time we've had a large enough sample to understand the genetic risk factors related to glioma, which opens the door to understanding a possible cause of these brain tumors," says co-senior author Melissa Bondy, Ph.D., professor in M. D. Anderson's Department of Epidemiology

The genetic variations identified are the first glioma risk factors of any type identified in a large study.

Read the News Release

Bondy and colleagues expect their findings eventually to help identify people most at risk for the disease and to provide potential targets for treatment or prevention.

For Bondy, the findings are particularly gratifying. "I've been collecting families and case studies since the early 90s," she says. "We have only just begun to understand the causes of brain tumors. Our findings give reasons for hope for those who might be affected and an incentive for a more comprehensive investigation of what has been a mysterious disorder."

Gliomas, deadly tumors that form in the supportive tissue of the brain and spine, account for about 80% of all primary malignant brain tumors, with about 22,000 new cases and 13,000 deaths annually in the United States.

Investigators at the Institute of Cancer Research in the United Kingdom were co-leaders on the study, which also included teams from France, Germany and Sweden.

New research by Ben Smith, M.D., adjunct assistant professor in M. D. Anderson's Department of Radiation Oncology, has proven true Yogi Berra's assertion that, "The future ain't what it used to be!"

Taking into account who's growing old in the United States and how many of us will be old by 2030, Smith projects a 45% increase in cancer diagnosis in general and a 99% increase in cancer incidence among minorities (compared with a 31% increase for non-minorities).

It's very important to note that the researchers aren't saying that anyone's risk for cancer will increase. In fact, their estimates hold the risk to be exactly the same as it is today. Rather, what they're saying is that the number of cancer cases will increase simply because the U.S. population is aging (and older people are more likely to get cancer), and because the proportion of minorities in the U.S. is increasing (so they will make up a bigger percent of the cancer cases in 2030 than they do now).

Among minority groups, expected increases in cancer incidence are:

• 64% for African-Americans
• 76% for American Indian/Alaska natives
• 132% for Asian/Pacific Islanders
• 142% for Hispanics

Currently, although minorities often have higher risk for some cancers, the actual number of minorities who have cancer is low because minorities as a group are younger than the white population and younger people are less likely to get cancer. However, the large group of middle-aged minorities today will make up the group of "old" people in the year 2030. At that time, minority populations will experience the double burden of higher cancer risk and older age. The result will look like an epidemic of cancer in this population. 

Why is this information important for researchers like me and dedicated, caring folks like you? Having a glimpse of the future means that we have time to put into place actions today that can significantly impact the rate of cancer, as well as deaths from cancer, for specific population groups. For example, because minorities are more affected by cancers of infectious origins such as liver cancer and cervical cancer, by implementing effective prevention, education and screening strategies today, we may be able to limit the cancer burden in this group in 2030.

Smith suggests vaccination programs for hepatitis B and human papilloma virus, chemoprevention with tamoxifen and raloxifene, social interventions such as tobacco and alcohol cessation that work for minority groups, and removing pre-cancerous polyps in the colon.

Finally, increasing minorities' participation in cancer clinical trials today will reap even more benefits for care in the future. It will help us to better understand the impact of race on how tissues respond to cancer treatment, the biology of cancer in different groups and effectiveness of cancer therapy for these groups.

Until a few years ago, only a handful of physicians and nurses -- and an even smaller number of women in the community at large -- had ever heard of a rare but fast-growing type of breast cancer, inflammatory breast cancer (IBC).

The birth of the Internet provided a vehicle for mass communication unparalleled in our history. Perhaps, like me, you were the recipient of the first e-mail alert with a subject line of "the breast cancer without a lump: what every woman should know." That first alert was composed by the mother of a young woman in her 30s who was losing her battle with inflammatory breast cancer.

For decades, women have been lulled into a false sense of security when it comes to breast cancer. That is if you perform monthly self-checks and have an annual mammogram screening after age 40, you'll be able to catch breast cancer in its early stages. These are important guidelines that every woman should heed, but inflammatory breast cancer doesn't play by conventional rules. What about "the breast cancer without a lump"?

Inflammatory Breast CancerIBC is particularly aggressive. The five-year survival rate for IBC is only 40%. (The five-year survival rate for all breast cancers combined is 87%.) It occurs in relatively young women. It's not uncommon to see women in their 30s to 50s in our Inflammatory breast cancer Clinic at M. D. Anderson. The cancer has often spread to the lymph system or beyond at the time of diagnosis. That's why it's so important for every woman to know the signs.

Inflammatory breast cancer appears on the skin of the breast. There's seldom a palpable lump. It may initially look like a bug bite or a breast infection, such as mastitis. The women in our IBC Clinic tell a similar story of noticing a small, red patch that spreads in a matter of days or weeks; a swollen, hot breast with no fever; and skin that is puckered or dimpled. If you notice these signs, don't delay getting to your physician. Your doctor may prescribe a round of antibiotics. If there isn't marked improvement after one course, pursue a referral to an IBC specialist.

So what's the good news here? While breast cancer as a whole will affect one in eight women in their lifetime, IBC is relatively rare. It accounts for about 2% to 6% of breast cancers. Our patients now have clinical trials for IBC that combine standard chemotherapies and targeted therapies like lapatinib. New agents are being tested in pre-clinical settings in our laboratories with more clinical trials set to open soon.

In M. D. Anderson's Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, our motto is "Teach it. Treat it. Beat it." We have assembled a team of clinicians, researchers and advocates who are passionate about raising awareness of inflammatory breast cancer, identifying tools for earlier diagnosis and new treatments that will mean better outcomes for our patients. Help us spread the word.

By Bayan Raji, Staff Writer

Keisha Huse was still adjusting to life as a new mom when she began to notice pains in her stomach. The first time, the pain lasted for an hour and didn't return for several weeks. But by the time her daughter was three months old, Huse was feeling the pains daily.

JulyFA1_2edit.jpgHer friend had a similar ache after childbirth that ended up being kidney stones, so Huse thought that might be her problem as well. But she hadn't completely stopped bleeding after giving birth, which led her doctor to believe the pain had another source.

"The doctor asked me if there was any way I could be pregnant, and I said it wasn't likely," Huse says. "But, he had me take a pregnancy test, and it came back positive."

Molar pregnancy discovered

Close to her six-week prenatal checkup, the pain worsened. Huse went to the emergency room, thinking something was wrong with her pregnancy. An ultrasound revealed Huse had a molar pregnancy that had to be removed.

In a molar pregnancy, grape-like cysts grow in the uterus after conception. The cysts usually contain tissue from the placenta and occasionally tissue from an embryo that did not develop.   

Molar pregnancies are rare, especially after live, healthy births. They are benign but sometimes develop into malignant tumors. They generally secrete the pregnancy hormone, human chorionic gonadotropin, which is why her doctor thought Huse was pregnant.

Cancer is surprise diagnosis

After the molar pregnancy was removed, Huse thought the ordeal was over. But before she left the hospital, the doctor called her in for a private discussion.

"A routine chest X-ray for admission showed nodules in my lung," Huse says. "I had a rare type of cancer called choriocarcinoma that had spread to my liver and lungs. To go from thinking you were pregnant to being told you have cancer -- with a 3-month-old baby at home -- was a shock."

Because one of her classmates from high school was treated for cancer at M. D. Anderson, Huse, who lives in Wichita Falls, Texas, more than 300 miles from Houston, decided to go there as well.

"I told the doctor I wanted a referral to M. D. Anderson," she says. "This condition is rare, and I wanted to see people who deal with it a lot."

Self-image is clipped

Before she started treatment, Huse faced an emotional struggle. She feared losing her hair, which had been long for years and which she considered one of her best attributes, during chemotherapy.

Knowing she probably faced its loss, she cut it to chin-length before she left home. But even with that pre-emptive move, she felt she was losing her identity when hair fell out. The hospital provided her with a wig, but it took some time to feel comfortable in it.
"I was known for my hair," Huse says. "For me, losing it took away my womanhood. I didn't feel pretty, and that was hard to deal with emotionally."

Treatment takes a toll

During the three months Huse was treated at M. D. Anderson, her mother, who also lives in Wichita Falls, stayed with relatives in Louisiana and kept the baby. Huse drove the two hours to visit when she could, but being away from her baby was difficult. 

Her chemotherapy routine alternated each week between once-a-week, three-hour treatments and three-day hospital stays. She got a break only when her white blood cell count was too low to receive chemotherapy.

Although she responded well to treatment, Huse grew tired of being far from home and her family. She requested that her care be transferred closer to Wichita Falls, where she continued to receive chemotherapy for another year. During this time, she came to M. D. Anderson periodically for check-ups. 

"After the transfer, chemotherapy took a different toll on my body," she says. "I was nauseated all three days each time I was in the hospital. I'd get too weak to even move."
July_FA1_1edit.jpgShe feels a new take on motherhood

Now 22, Huse has been cancer-free for more than a year. She believes her take on motherhood is quite different from what it would have been had she not gotten cancer. Her cancer and treatment affected her ability to bond and play with her new baby in the ways she once dreamed.

"I've always wanted a baby, and it was really hard to think that I wouldn't be there for her or watch her grow up," Huse says. "I learned to appreciate her more. I enjoy the smaller things more than I probably would have if I hadn't experienced this."

Experience brings strength

Huse says cancer helped her conquer a phobia of hospitals and doctors. Now, she hopes to be a pediatric nurse one day.

"When I had cancer, I had to be a strong person," she says. "If I showed a sign of weakness, it worried my mom. I didn't want my baby to see me scared either. Now I think I'm much stronger."

Related article:
Q&A: Gestational Trophoblastic Cancer


Choriocarcinoma (Medline Plus)

Gestational trophoblastic tumors treatment (National Cancer Institute)

Gestational trophoblastic disease (M. D. Anderson)

Department of Gynecologic Oncology (M. D. Anderson )

Read more Feature Stories from Cancerwise

Gestational trophoblastic cancer (GTC) is a rare, yet highly treatable, disease. Although it is sometimes referred to as gestational cancer, it usually does not coincide with a successful, long-term pregnancy.

Karen Lu, M.D., professor in the Department of Gynecologic Oncology at M. D. Anderson, answers some questions about this unusual cancer.

What is GTC?

GTC is a rare cancer in which malignant cells grow in the tissues that are formed in a woman's uterus following conception (the joining of sperm and egg). The uterus is the hollow, pear-shaped organ where a fetus grows.

Most frequently, GTC develops after a woman experiences a miscarriage or molar pregnancy.

A molar pregnancy, which occurs in one of 1,000 pregnancies in the United States, is an abnormality of the placenta that leads to a growth of abnormal tissue when an egg is fertilized. A developing embryo is rarely present, but the tissue grows rapidly and appears in grape-like cell clusters.

Rarely, GTC can occur after a live birth. This is called choriocarcinoma.

GTC generally affects women younger than 20 and older than 40.

What are the symptoms of GTC?

The main symptom is abnormal vaginal bleeding, especially after a miscarriage, but also after a molar pregnancy or live birth. Abnormal bleeding would be defined as bleeding between normal menstrual periods or bleeding almost every day instead of having menstrual periods.

If a woman has a molar pregnancy, she usually will be monitored afterward to make sure she doesn't develop GTC.

How is GTC diagnosed?

Most often, a woman notices irregular bleeding and visits her doctor, thinking maybe she's pregnant. The physician may test the patient's level of human chorionic gonadotropin (hCG), which is elevated in pregnancy and in GTC.

If the hCG level is high, the doctor probably will perform an ultrasound to determine if the pregnancy is normal or molar, or if tumors are present.

What is the treatment for GTC?

Once a woman is diagnosed with GTC, CT (computed tomography) scans are performed to determine if the tumor has spread beyond the uterus.

If the tumor has not moved outside the uterus, the patient typically has chemotherapy until hCG levels return to normal. Levels are monitored for about a year to make sure they remain normal.

If GTC has spread beyond the uterus, treatment may include chemotherapy and/or surgery.

What is the prognosis for women diagnosed with GTC?

GTC has a cure rate greater than 90%, depending on the tumor's sensitivity to chemotherapy.

The ability to measure hCG levels has helped increase survival in recent years.

Women with GTC have higher rates of survival when they are referred to specialized centers with experience in treating this rare disease.

Does GTC or its treatment affect a woman's ability to have children?

To treat this cancer, doctors typically don't need to remove the uterus. Many women go on to have children after treatment.

What are some risks associated with the disease?

Because GTC can occur in women over 40, some patients may think they're going through menopause when they experience irregular bleeding and not visit their physicians.

Also, because GTC isn't very common, it's often misdiagnosed. Women of reproductive age can request their physician measure their hCG levels if they're concerned.

What should a woman do if she is diagnosed with GTC?

Once a woman is diagnosed, it's in her best interest to go to a specialized center that frequently sees cases of GTC. Overall, GTC is easier to treat and monitor than other cancers, but certain subtypes can be aggressive and more difficult to treat.

Related article:
New Mom Finds Strength in Cancer Ordeal

M. D. Anderson resources:

Karen Lu, M.D,

Gynecologic Oncology Center

What is Gestational Trophoblastic Disease? (American Cancer Society)

Read more Feature Stories from Cancerwise

By Mary Brolley and Bayan Raji, Staff Writers

When people are diagnosed with lymphoma, they probably aren't thinking of ways to help prevent or treat the disease. However, a tissue donation to M. D. Anderson's Lymphoma Tissue Bank could help researchers do just that.

The purpose of the bank - and others like it - is to collect, process and store tissue samples for research. The samples then are distributed to research teams within M. D. Anderson as well as investigators collaborating with the institution.

Lymphoma is a general term for cancers that develop in the lymphatic system, the tissues and organs that produce, store and carry white blood cells.

Tissue aids research

The more researchers learn about lymphoma, the more they realize that each patient's disease progresses differently.

Researchers hope to advance treatment of the disease and help patients live longer.
Using the donated tissue, they will study how lymphoma develops and try new drugs on tissue samples before testing them in people. This will allow drugs that are likely to have the best chance of success to be moved rapidly from the laboratory to the clinic for the benefit of patients.

Rare lymphomas need investigation

Two types of lymphoma, follicular and diffuse large B-cell, account for about 50% of lymphoma cases diagnosed. The tissue bank is especially important for finding out more about the less common forms of lymphoma.

Researchers hope patients with less prevalent forms of the disease such as Hodgkin's lymphoma, T cell lymphoma, marginal lymphoma, Burkitt's lymphoma or people with AIDS (acquired immune deficiency syndrome) will benefit from increased research on potential treatments.

Patients are informed about process

About 400 people have enrolled in the M. D. Anderson Lymphoma Tissue Bank over the past year, and the numbers continue to grow, says Sattva Neelapu, M.D., assistant professor in the Department of Lymphoma and Myeloma at M. D. Anderson.

Doctors make it a point to inform patients about the bank and its potential value. Established patients are approached when they visit the cancer center for procedures. New patients learn early in their treatment about the bank and how they can contribute.

"We discuss tissue donation with new patients on their first visit," Neelapu says. "They have the option to accept or decline, but the majority are eager to donate their tissue for research."

Process is not inconvenient

Tissue samples for the bank are taken from biopsies performed during the diagnostic process, which means patients are not inconvenienced with special procedures to retrieve samples, Neelapu says.

"We don't stick patients simply to get tissue for the bank," he says. "At no point do we do a procedure just for research purposes."

Typically, only a portion of the tumor or tissue sample is sent to the diagnostics lab, while the remaining parts are discarded. If a patient agrees to donate tissue to the bank, left over specimens are used for research.

Research has wide-ranging effects

The advances made possible because of the Lymphoma Tissue Bank will help patients everywhere with this disease, not just those at M. D. Anderson.

"This bank is beneficial for patients, the institution and research in lymphoma in general because it will help us better understand how lymphoma starts and grows and help us develop new therapies," Neelapu says. "It also will help us develop a larger coalition with other researchers and institutions conducting lymphoma research."

A new informational brochure helps explain the process and purpose of tissue donation to patients. Neelapu hopes it will encourage patients to donate tissue.

"Great strides are being made in the treatment of this difficult disease," he says. "These advances are possible because researchers have been able to conduct research in the lab using lymphoma tissue. The more tissue we have to work with, the more advancements we can make."

M. D. Anderson resources:

Hodgkin's Disease

Non-Hodgkin's Lymphoma

Sattva Neelapu, M.D.

Department of Lymphoma and Myeloma

Lymphoma and Myeloma Center

Other resources:
Overview: Lymphoma, Non-Hodgkin Type (American Cancer Society)

What You Need to Know About Lymphoma (Lymphoma Research Foundation)

By Bayan Raji, Staff Writer

The eyes have been called the windows to the soul, but the hands and feet are often the first parts of the body to experience something, perhaps the softness of a blanket or hot sand on a beach.

The importance of hands and feet make them the focal point of reflexology, a healing art historians believe was used first in China more than 5,000 years ago. It focuses on pressure points of the hands and feet and can be used by anyone, but it may be especially beneficial to cancer patients.

ReflexologyPressure applied to hands, feet
Reflexology may help relieve symptoms often related to cancer treatment such as nausea, insomnia and stress. The technique also is believed to have a generally beneficial effect on a person's health and well-being.

Reflexology therapists use their hands - usually their thumbs or forefingers - to apply pressure to areas of the hands and feet that they believe are connected to specific zones of the body. Stretching and movement techniques also may be used. They may open or close the session with a gentle hand or foot rub.

Symptoms may be helped

Margaret Harle, a registered nurse, holistic health consultant and reflexologist, teaches classes about reflexology to patients and caregivers at M. D. Anderson's Place ... of wellness. She answers questions about the technique and demonstrates reflexology for those who are interested in using it at home.

Harle says that during private sessions reflexologists generally work on the hands or feet for 30 to 45 minutes. Most patients find the sessions relaxing, and many experience temporary symptom relief.

Some patients notice mild temporary, uncomfortable after-effects, including:

    * Nausea
    * Fatigue
    * Need to urinate more often

Check with your doctor first
Reflexology should be part of a comprehensive health care plan, Harle says. Some people with certain side effects of cancer or cancer treatment, including lymphedema and neuropathy, should avoid reflexology. Be sure to check with your health care provider.

Reflexology should not be considered an alternative to medical treatment.

M. D. Anderson resources:
Integrative Medicine Program

Other resources:
Manipulative and Body-Based Practices: An Overview (National Center for Complementary and Alternative Medicine)

By Mary Brolley, Staff Writer

A cancer diagnosis may feel like a one-way ticket to a strange country. No passport, no map, no directions. And, at first, patients don't even speak the language.

Once treatment is complete, survivors may feel relieved, but they frequently are drained and uncertain as well. They may have questions about what's next, and it's likely they are more determined than ever to be conscious of their health and emotional state.

To help them -- and their caregivers -- navigate the physical, emotional and practical challenges of life after cancer treatment, the Patient Education Office at M. D. Anderson has developed a comprehensive booklet that's now available online.

Survivorship_bookletAccess roadmap for survival

"Survivorship: Living With, Through and Beyond Cancer," offers an overview of life after a cancer diagnosis and treatment. Whether patients have questions about how to keep themselves as healthy as possible, want to know how to deal with treatment side effects or how best to weather the financial strains cancer treatment may bring, this information points them in the right direction.

A list of survivorship resources helps patients find answers to questions or concerns about the physical, psychosocial, emotional or spiritual impacts of a cancer diagnosis and treatment. This section also indicates whether patients need referrals to seek these services.

"Because survivors may be overwhelmed with options and questions, we wanted to make it easier for them to find the information and resources they need," says Julie Bradford, program manager for communications in the Patient Education Office.

Online content expands audience

Although this booklet is available at M. D. Anderson, Bradford says making it available online ensures that patients everywhere have access to it.

"The Internet has broadened survivors' research options -- and our reach -- incredibly," she says. "We're so happy this information is accessible to people all over the world."

 Download and print the survivorship booklet. (PDF)

M. D. Anderson resources:

Cancer Survivorship

Patient Education Office

Other resources:

Living With and Beyond Cancer (U.S.News and World Report)

Survivors After Treatment (American Cancer Society)

The Cancer Survival Toolbox (National Coalition for Cancer Survivorship)

Read more Feature Stories from Cancerwise

Metastatic Colon Cancer Survival Jumps Dramatically
Almost a Third of Patients May Live Five Years

Novel chemotherapy and biological agents, combined with advances in liver surgery, have increased five-year survival rates for metastatic colorectal cancer from 8% to 30% in the past 20 years.

Acupuncture Eases Radiation-Induced Dry Mouth
Ancient Technique Shows Promise
The traditional Chinese medical technique of acupuncture may safely help patients whose radiation treatments cause extreme dry mouth, or xerostomia.

"The quality of life in patients with radiation-induced xerostomia is impaired profoundly," says Mark Chambers, D.M.D., professor in the Department of Dental Oncology and the study's senior author. "Conventional treatments have been less than optimal, providing short-term response at best."

Genetic Variants Predict Bladder Cancer Recurrence, Survival
SNPs Play Roles After Standard Treatment

Variations in genes that modulate inflammation in the body can influence survival rates and recurrence in patients with non-muscle invasive bladder cancer (NMIBC) who are treated with one of the most common therapies for this disease.

In this study of 596 patients at M. D. Anderson, Yang and his colleagues evaluated 59 gene variations called single nucleotide polymorphisms (SNPs) in 35 major inflammation genes to try to find the roles they might play in preventing or facilitating recurrence.

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