Fine-Tuning Cells to Tune Out Disease: Immune System Discoveries Spur Hope

To understand what causes type 1 diabetes (T1D), imagine a spy novel. It starts with a hero, the T-cell, that roams your body like James Bond. The T-cell hunts down enemies — bacteria and viruses — and snuffs them out. Then something goes terribly wrong: The hero becomes a villain.

Like a double agent, T-cells can turn against your body and attack your pancreas, triggering T1D. It keeps attacking for years, methodically destroying your ability to produce insulin and control blood sugar. Your T1D becomes ever more debilitating.

Fortunately, there’s hope: One of Benaroya Research Institute’s real-life heroes, Alice Long, PhD, is moving closer to a therapy that makes the enemy T-cells so exhausted they surrender.


BRI researcher Alice Long, PhD

“We think it could be possible to make the T-cells say ‘we give up, we’re too tired to keep attacking the pancreas,’” Dr. Long says. “That could slow down T1D or maybe even stop it.”

This approach of manipulating T-cells to stop disease could extend far beyond T1D. That’s why Dr. Long is teaming up with other BRI researchers, including BRI President Jane Buckner, MD, to study the machinery inside these cells more closely than ever before.

“This could reveal ways to dial T-cells down to stop autoimmune disease, or dial them up so they attack cancer,” Dr. Buckner says. “It’s a new frontier of immune research and BRI is excited to be at the forefront.” 

T-cell Discoveries

Dr. Long has dedicated her career to finding better therapies for the millions of people with T1D. The best available treatment is to inject insulin. Even then, T1D increases the risk of serious health issues like heart disease and stroke.

“There’s a desperate need for therapies that protect the pancreas so it can keep producing natural insulin, because that helps people with T1D stay healthier and have fewer complications,” Dr. Long says.

Dr. Long believes that understanding a phenomenon called “T-cell exhaustion” could unlock these therapies. Several years ago, researchers discovered the body is home to exhausted T-cells, which are alive but have stopped attacking. Everyone has these exhausted cells. But subsequent research showed that people with autoimmune disease who have higher numbers of these cells also have less severe disease and fewer complications. Then Dr. Long and Peter Linsley, PhD, made a key discovery of their own.

They showed that T1D progresses more slowly in people who have higher numbers of exhausted CD8 T-cells. They also found that a drug called teplizumab increased exhausted CD8 T-cells in most individuals. Even better, BRI researchers led a study that showed treatment with this drug delayed the onset of T1D by approximately three years in people who were susceptible to the disease.

“Those were ‘a-ha moments’ — we started to think, maybe it’s possible to create a therapy that exhausts these cells and stops T1D,” Dr. Long says. “But first we needed to understand these cells in much greater detail.”

Fine-Tuning the Immune System

Dr. Long recently received a $2.6 million National Institutes of Health grant to investigate why CD8 T-cells become exhausted and how this influences T1D. She’s also collaborating with Dr. Buckner and Erik Wambre, PhD, on an NIH-funded project that looks at T-cells in cancer patients.

People with cancer have the opposite problem as people with T1D and other autoimmune diseases. In cancer, T-cells should attack cancer cells, but something about cancer leaves them too exhausted to attack. Drugs called checkpoint inhibitors can nudge those cells back into attack mode. But those drugs can push T-cells into overdrive, until patients end up with symptoms similar to autoimmunity.

“If we can understand the process that leads to autoimmunity in these patients, it could help us understand the biological dial that controls how much T-cells attack,” Dr. Buckner says.

The BRI team’s vision is to be able to control both sides of the T-cell equation. This means they could adjust cancer therapies to prevent autoimmune attacks, or create therapies that exhaust attacker cells and stop autoimmune disease.

“We’re getting closer to being able to turn the immune system up or down depending on a patient’s needs,” Dr. Buckner says, “And that means we’re getting significantly closer to improving the lives of people with everything from T1D to cancer, and maybe even to stopping those diseases altogether.”

A version of this story originally appeared in the Benaroya Research Institute Autoimmune Life Blog

New Research Applies the Brakes to Type 1 Diabetes

A prevention study involving diabetes researchers and volunteers at Benaroya Research Institute at Virginia Mason (BRI) showed a drug that targets the immune system — Teplizumab — can delay type 1 diabetes up to three years in children and adults at high risk.

“This is great news for relatives of people with type 1 diabetes, who are at 15 times greater risk of the disease than the general population,” said Carla Greenbaum, MD, director of Interventional Immunology and the Diabetes Research Program at BRI.

Samples collected during the trial are being studied to help researchers understand why certain people responded to the drug better than others. Next, TrialNet researchers hope to conduct additional studies to look for ways to extend the benefits of the drug.

New Insight into Disease Progression

BRI Alice Long

BRI researcher Alice Long, PhD

When some people are diagnosed with type 1 diabetes, the disease progresses so quickly that their pancreas stops making insulin within a year. For others, the process is slower and their disease easier to manage. BRI research revealed that it’s possible to identify the “fast progressors” early and match them with treatments that help keep them healthy for longer.

BRI’s Alice Long, PhD, and her colleagues made the discovery that opened the door to potential new treatment strategies for type 1 diabetes. In a paper published in Journal of Clinical Investigation, the researchers identified important differences between fast progressors and people whose disease progresses much more slowly. Dr. Long’s team showed that slow progressors have higher levels of exhausted CD8 T cells — cells that are worn out from attacking the pancreas. The discovery could lead to a test that identifies how quickly individual patients will lose their ability to make insulin.

“Doctors may be able to give ‘fast progressors’ a therapy that’s going to slow down the attacker cells or maybe even stop them,” said Dr. Long, a BRI principal investigator. “For this group of people with type 1 diabetes, that would prolong their ability to make insulin, which makes their lives much easier and significantly reduces their long-term health risks.”

A version of this story originally appeared in the Virginia Mason Health System Annual Report. 

Exciting Developments for Pancreatic Cancer Care

**By Flavio G. Rocha, MD**

After successful treatment for pancreatic cancer, one of our patients shared her story. Life after cancer is not normal, she said, it’s better than that. She talked of being inspired by the dedication of the Virginia Mason team. As a member of this team, a cancer surgeon and a clinical researcher, I am inspired by the progress we and other organizations are making toward better treatments for this disease. Working together to discover new therapies and the potential for early detection, the future of treating pancreatic cancer has never felt more hopeful.

Today Virginia Mason sees almost a third of all pancreatic cancer patients in Washington state, with decades of experience delivering care as a multidisciplinary team. This collaboration across specialties – along with advances in imaging, surgical techniques, specialized treatment and safety protocols – contributes to a doubling of the overall survival of our patients compared to the national average, as reported by the National Cancer Institute’s Surveillance, Epidemiology, and End Results Program.

researchVirginia Mason is also invested in world-renowned medical research with Benaroya Research Institute (BRI), offering patients access to clinical trials investigating new therapies for all stages of pancreatic cancer. As a BRI affiliate investigator, I see a new wave of disease-fighting possibilities ahead, based on the latest research involving cancer cell microbiology, genetic testing and immunotherapy.

Reach Goal: Early Detection

Despite improvements in treatment, an estimated 46,000 people in the U.S. will die of pancreatic cancer this year. That’s because 90 percent of cases are diagnosed in later stages, when the cancer has already spread to other tissues or organs or requires preoperative therapy to reduce tumors. Virginia Mason, in partnership with BRI and other research collaboratives, is focused on looking inside the pancreatic cancer cell to identify biomarkers that signal a precancerous condition.

A specific protein, for example, was found in a clinical trial to be significantly elevated in the pancreatic fluid of patients known to have premalignant lesions. These results suggest that testing the fluid for this biomarker could detect disease in patients at increased risk, before becoming pancreatic cancer. Other research around early detection focuses on developing special blood tests, diagnostic imaging and other screening tools to find disease at its earliest stages.

Hereditary Cancer Testing

In July 2018, the National Comprehensive Cancer Network (NCCN) issued a new guideline that all individuals with a diagnosis of pancreatic cancer must meet criteria for hereditary cancer testing. Studies suggest up to 10 percent of pancreatic cancer is caused by an inherited mutation in BRCA1 or BRCA2, the so-called breast cancer genes. Other genetic mutations have been linked to an increased risk of pancreatic cancer as well.

Is there a benefit in genetic testing if the patient already has pancreatic cancer? Yes, for two reasons:

  • Knowing about an inherited genetic mutation may help direct treatment decisions. BRCA-associated cancers, for example, are known to respond to certain treatments, including specific types of chemotherapy. This concept of “personalized medicine” is expanding through clinical trials of other agents that target cancers linked to genetic mutations.
  • Identifying a mutation can be valuable knowledge for family members, who can choose to be tested and learn if they are at higher risk for developing certain cancers. That’s because the same mutation that is linked to pancreatic cancer is also associated with breast, ovarian and other cancers. Family members who test positive can engage in screening or risk-reducing strategies for other forms of cancer, as available.

Boosting the Body’s Immune System

Leveraging the power of the body’s own immune system to fight cancer is the science behind immunotherapy, variations of which are already prescribed by oncologists to treat a variety of cancers. While success has been limited using immunotherapies in the treatment of pancreatic cancer, ongoing clinical trials are testing multiple forms of the therapy, including pancreatic cancer vaccines (designed to “program” the immune system to attack cancer cells), and immune checkpoint inhibitors (shown to reactivate immune cells shut down by cancer cells). Other forms of immunotherapy utilize modified viruses to infect tumor cells, or modifications of the body’s own cells to disrupt cancerous activity.

The Future of Research is Now

Virginia Mason is one of 12 clinical trial sites selected nationwide by Precision Promise, the Pancreatic Cancer Action Network’s groundbreaking initiative to improve patient outcomes and double the pancreatic cancer survival rate by 2020. Starting this year, patients will be able to enroll in Precision Promise through the participating sites, accessing trials of multiple novel therapies alongside standard care approaches.

Through Precision Promise, clinical outcomes data will be continuously tracked and analyzed, accelerating findings that can be shared across the trial sites. Analysis methods, including the use of genomic data, will be matched to patients’ responses to therapy to quickly identify effective treatment options. As breakthroughs emerge, Precision Promise will adapt clinical programs to help get successful therapies out to patients faster than traditional research models.

What Keeps Us Going? Our Patients

The pancreatic cancer survivor who shared her story described the joy of seeing her daughter graduate, and teaching her son how to drive. As physicians we are privileged to not only treat disease with our best skills and knowledge, but to nurture hope in our patients that they will return to the lives and people they love. We have seen the pancreatic cancer survival rate increase 3 percent during the last three years, and momentum is building. The time for changing everything we know about diagnosing and treating this disease starts now.

Flavio Rocha, MD
Flavio G. Rocha, MD, has advanced training in surgical oncology and specializes in liver, biliary tract and pancreatic cancer. He is director of research in the Digestive Disease Institute at Virginia Mason and an affiliate investigator at Benaroya Research Institute. Dr. Rocha practices at Virginia Mason Hospital and Seattle Medical Center.

Immune System Discovery May Stop Breast Cancer

The study of a protein, critical in causing asthma, allergies and other diseases, has led scientists at Benaroya Research Institute at Virginia Mason (BRI) to discover a new strategy for stopping breast cancer.

BRI researchers Emma Kuan, PhD, and Steven Ziegler, PhD, have pinpointed how the protein, called thymic stromal lymphopoietin (TSLP), helps breast cancer tumors survive and grow. Even more significant, the researchers showed that blocking TSLP can significantly inhibit the growth of breast tumors and halt metastasis to the lung. This discovery opens the door to new strategies that could stop breast cancer tumors from growing and spreading. It may also be applied to other tumors that involve TSLP.


Steven Ziegler, PhD                                          Emma Kuan, PhD

“Breast cancer becomes especially dangerous once it spreads to other parts of the body,” Dr. Kuan says. “Our work suggests that blocking TSLP could prevent this from happening and potentially save the lives of women worldwide.”

The research was published recently in Nature Immunology. TSLP was discovered 15 years ago by the Ziegler Laboratory, as well as other labs, to initiate the inflammatory cascade that leads to the development of asthma, allergies and other diseases.

How TSLP Helps Tumors

Researchers had previously found elevated TSLP levels in several different tumor types, but its role in tumor biology was unclear. Drs. Kuan and Ziegler solved this mystery by using preclinical models to investigate what happens to breast cancer tumors when TSLP is taken away.

Their research revealed that the tumors didn’t grow nearly as large – or metastasize nearly as much – when they didn’t have access to TSLP. In fact, the breast cancer cells died without access to TSLP, resulting in markedly smaller tumors and a lack of lung metastases, compared to tumors where TSLP was present.

“The tumors can get started without TSLP, but they need it in order to stay alive and metastasize through the body,” Dr. Ziegler says.

Hijacking Immune Cells

Once the researchers determined that TSLP was critical, they set out to uncover how it worked – and became the first to discover that tumors turn immune cells into accomplices that express TSLP. Importantly, the researchers found that the same cells that make TSLP in the models also make TSLP in human breast cancer patients, and human breast tumor cells respond to TSLP in the same way.

Stopping Tumor Growth

When Drs. Kuan and Ziegler used an antibody to block TSLP, it stopped tumors in their tracks – even when they had already started growing. Within six weeks, the tumors had shrunk significantly, more of their cells were dying and they had stopped spreading to the lungs. This suggests that anti-TSLP therapy could work in human patients with existing tumors.

“Blocking TSLP could potentially contain not just breast cancer, but many other tumors that have elevated TSLP – including pancreatic cancer, cervical cancer and multiple myeloma,” says Dr. Kuan.

A drug that blocks TSLP has already been developed and initial trials have shown that it’s safe in patients with asthma, so scientists are hopeful clinical trials could be launched for cancer patients in the relatively near future.

“We’re currently working on a better way to block only the TSLP that helps tumors,” Dr. Kuan says. “And we are really hopeful that this could become a viable strategy for containing tumors long-term, without interfering with TSLP in other healthy cells.”

New Cancer Biorepository

For their research, Drs. Ziegler and Kuan used samples from BRI’s new biorepository, the Virginia Mason and Benaroya Research Institute Tumor Repository (VM BRITE). The biorepository houses the medical history and blood and tumor samples of research participants with a variety of cancers.

“As BRI studies the immune system and tries to understand why it veers off course, we learn how it relates to other diseases such as cancer,” says BRI President Jane Buckner. “We want to pursue these discoveries to improve the lives of people with autoimmune diseases, cancer and hopefully many other diseases.”

A version of this story originally appeared in the Benaroya Research Institute Autoimmune Life Blog


Self-Advocacy for Autoimmune Disease Patients: A Conversation with Judi Rising and Tracey Barnes

Judi Rising and her daughter Tracey Barnes know a lot about advocating for people living with autoimmune diseases. Judi is co-founder of the Autoimmune Advocacy Alliance (A3 Alliance) and has spent years educating local and statewide communities about autoimmune diseases. And Tracey, who has lived with multiple sclerosis (MS) for 11 years, often shared her advice on self-advocacy for autoimmune patients as a former

Judi and Tracey

Judi Rising (left) and her daughter, Tracey Barnes

spokesperson for Biogen. Twenty years ago, however, they knew next to nothing about autoimmune diseases.

Judi and Tracey first learned about autoimmune diseases when Tracey’s brother Pat was diagnosed first with Hodgkin’s disease, then with idiopathic thrombocytopenic purpura (ITP), a rare autoimmune blood disease. Six weeks after his ITP diagnosis, Pat passed away. “We had heard the words ‘autoimmune disease’ prior to this, but had no details of any kind and of course no understanding of the impact it could have,” Judi says.

After Pat’s death, Judi and her husband Dick knew they had to spread awareness about autoimmune diseases. They founded “Pat’s Fund,” to educate others about autoimmune diseases, which grew into the A3 Alliance with the support of Benaroya Research Institute at Virginia Mason. Tracey’s own journey with MS has taught the entire family about what self-advocacy as an autoimmune patient looks like, as well as how family and friends can support loved ones living with one of these 80+ chronic diseases.

We recently sat down with Judi and Tracey to hear their advice on how to advocate for yourself and others living with autoimmune diseases.

Tracey, what does self-advocacy mean to you as a patient living with an autoimmune disease?  

Tracey: Self-advocacy begins with your attitude and how you look at things —attitude is absolutely everything.

What I’ve discovered is that people who’ve been diagnosed with MS go one of two ways. They either say, ‘My life is over and I’m going to give up right now. I don’t care. I’m angry, and I’m scared.’ Or, they say, ‘Okay. This is something that’s in my life, and I’m going to do the best I can to deal with it and move on.’

If I’m having a bad day, I sit down and say, ‘This is what you have—but look at all your blessings, and look at all you’ve been given in life. Are you going to give into this?’ I do not allow myself to go down the slippery slope of thinking about, for example, the fact that I don’t have any children and don’t know who will take care of me when I’m older. Instead of doing that, I think it’s very important to focus on a few things you know will get you out of the darkness.

Self-advocacy is also a process of asking questions and learning. When you don’t understand something about your disease, your medication, or your symptoms, ask the question again.

What does self-advocacy look like at the doctor’s office?

Tracey: No question is dumb—don’t be embarrassed to ask questions. Don’t think, ‘The doctor is going to think I’m dumb, or I’m going to hurt their feelings.’ This is your life. In terms of anything you don’t understand, which is going to be 90 percent of what the doctor tells you, write it down or ask about it. It is so vitally important. For example, when I was first diagnosed, I was given the option to begin taking one of seven or eight different drugs. I didn’t feel prepared to make a choice, but I did. Little did I know the drug that I should have gone on was one that had a huge risk factor—so I had just dismissed it. If I had chosen that drug, I wouldn’t be in the situation I’m in right now [walking with forearm crutches]. If I’d known what I know now, I would’ve said to that nurse, ‘I don’t get it, I don’t know what drug to use. You’ve got to help me.’

Judi: If you have a question that your doctor can’t answer, you can also ask for a referral to a specialist or a system with specialists, like Virginia Mason or the University of Washington. We hear story after story about people who are misdiagnosed, sent to the wrong doctor, or not taken seriously by their primary care physician. Don’t be afraid to say ‘I appreciate everything that you’ve told me, and I’d like to hear from someone else. It’s nothing against you, I just want to hear a second opinion.’ There’s nothing wrong with that.

Tracey: It’s also really important to bring someone with you to your appointments. At one point, I took my mom or my husband to all my appointments because they both had a better understanding of the disease, and I wanted a second set of ears. When you start to feel rushed by the doctor, you need to say, ‘I’m feeling rushed. I don’t understand this. When or who can I talk to for more information?’ It’s so important.

How do you build and leverage support networks?

Judi: With regards to building community, support groups look great on the surface but can be really difficult to keep positive. When people don’t have anyone to share their story with, they see a group of people who understand what they’re going through, and sometimes it turns into a gripe session. You have to have someone in the group who helps keep the session positive.

I’ve seen that oftentimes, friends can be even better supporters than family members. It’s perfectly fine to make your support system your friend. If family doesn’t work for you as a support system, seek a friend because they may be more understanding and supportive than your family will. The breakdown of support within families is common, not uncommon. Sometimes, family wants to pretend that the disease is not there.

Tracey: For example, I have a friend who I can call and say, ‘Will you come down to the house and just let me talk?’ And she does. She’s a great friend.

What would you tell people who have been recently diagnosed?

Tracey: I wish there was a way to communicate to people who are newly diagnosed that there is help out there. You can be very positive and keep going in your life. I don’t think that is as well-known as it should be.

Judi: One of the really scary things for a lot of people when they’re first diagnosed is that they go online and get the message, ‘no cures.’ And unfortunately, in most people’s minds ‘no cures’ equates to incurable.

That really isn’t true, in the sense that most autoimmune diseases today do have treatments that can pretty much stop a disease from progressing. If you get on the right path, they can be stopped. And that isn’t exactly the same as incurable.

There are some internet sites that give good information, like Johns Hopkins Autoimmune Research Center’s website, and the Cleveland Clinic’s website as well as their page on understanding autoimmune diseases. In addition, there are some very good books to read like Living Well with Autoimmune Disease by Mary J. Shomon, and The Autoimmune Epidemic by Donna Jackson Nakazawa.

Most importantly, once a person has a diagnosis and a treatment (if available) they should begin to talk with others who have the same disease to find out how they deal with their issues for a better living experience. It is very important for people living with autoimmune diseases to reach out, share, and discuss their experiences.

A version of this story originally appeared in the Benaroya Research Institute Autoimmune Life Blog.

Meet the Dog Who’s a Weapon Against IBD

Jenn White has a secret weapon for coping with inflammatory bowel disease (IBD) – A French bulldog-Boston terrier mix, named after a rock legend: Jagger.

Jagger is more than Jenn’s emotional support animal, he’s a kindred spirit who also suffers from IBD.

“I applied to adopt dogs several times for over two years and it wasn’t working out. I was about to give up for a bit…then I came across Jagger and knew I needed him,” she says. “After a conversation with his vet about his digestive issues and diet, I made sure they knew I had similar problems and that he would be in great hands.”

Follow @Jagger_McFrenchie on Instagram

Jenn White and her dog, Jagger, help each other cope with inflammatory bowel disease.

IBD strikes when the immune system attacks the intestines, causing inflammation, abdominal pain and bleeding. As Jagger can testify, these problems are not unique to humans, and they occur at least as frequently in many animals as they do in people.  While many different types of IBD have been described in different animals, in humans it comes in two main forms: Crohn’s disease and ulcerative colitis.

Jagger and Jenn have been fighting IBD together since February of 2015, when she adopted him as a nine-month-old puppy. At the time, Jagger was malnourished and struggling with everything from incontinence to a high white blood cell count. But his route to recovery, though daunting, did not discourage Jenn at all.

“It was so sad to see him in pain,” she says. “But I knew he had tummy issues, and I knew I could handle it.”

Road to Recovery

Jagger’s road to recovery included a probiotic diet and anti-diarrheal medication. Once he felt better, Jenn decided to register him as an emotional support animal. She met with a trainer twice a month for a year, and they motivated Jagger with treats and taught him the commands required for certification: “sit,” “stay,” “lay,” and understanding his name.

“Jagger learned it all and when he needs to go to the bathroom, he knows to wait patiently at my front door,” she says. “The only times he has accidents is when he’s flaring and can’t hold his bowels.”

When Jagger is sick, Jenn draws upon her personal experience of following an IBD-conscious diet. If she notices signs of a flare, like vomiting or blood in his feces, she changes his diet. That may involve adjusting the consistency of his food or having him fast. And she does this all while managing her own, sometimes similar, symptoms.

“I’d say the biggest difference between our IBD experiences would be that Jagger rarely ever has fatigue, and I certainly do,” she says. “He is always ready to play!”

Enduring a Flare

Another key difference between Jenn and Jagger is that her IBD treatment is a lot more complicated. Jenn’s treatment has included several immunotherapy drugs and bowel surgery, and she chooses to follow a gluten-free, dairy-free and soy-free diet to try to keep her digestive tract in balance. Her treatment is guided by James Lord, MD, PhD, a Virginia Mason gastroenterologist and BRI principal investigator who leads several IBD studies.

Jenn, who works as an e-commerce buyer for Nordstrom Rack, said Jagger senses when she’s not feeling well – and responds by being gentler and more attentive. During the summer of 2016, Jenn had to take medical leave and was hospitalized four times when she suffered an extreme flare. During the flare, she made bathroom trips over ten times a day – but each time, Jagger waited for her behind the restroom door.

“I was so depressed, but Jagger’s sweet face brought me joy. It forced me to keep a routine and not fall into being unsocial,” she says. “And because I have to take him outside, he keeps me on a schedule, which is super important to managing chronic illness. He gives me someone else to focus on so I don’t spin about in my own struggles. I need him and he needs me need him and he needs me.”

Supporting IBD Patients

Jenn, who is currently in remission, volunteers for the Crohn’s and Colitis Foundation and sits on its Northwest Board of Trustees. She likes to bring pictures of Jagger to Camp Oasis, the Foundation’s summer program for children with IBD.

Jenn says it brightens kids’ spirits when they see a dog who’s just like them, and she also brings Jagger when she visits friends who are hospitalized for IBD.

One of her friends “absolutely lit up when Jagger walked in the hospital room,” she says.

BRI and Virginia Mason are involved in numerous studies to help us understand IBD and explore new treatments. View our currently enrolling studies here, or join the Clinical Research Registry to get connected with study opportunities.

A version of this story originally appeared in the Benaroya Research Institute Autoimmune Life Blog and  fall newsletter. 

Awareness and Surveillance: Critical Tools in the Fight Against Anal Cancer

**By David Aboulafia, MD**

Anal cancer is a subject most people would rather not discuss, because of its anatomical location, along with an unfortunate stigma attached to the malignancy. Although tragic, actress Farrah Fawcett’s openness about her diagnosis helped create much-needed public awareness during her battle with the disease, which she lost in 2009 at the age of 62.

stop-cancerCloser to home, a 51-year-old White Center resident named Ed was impressed with Fawcett’s openness and advocacy. He now feels very fortunate that he listened to his physician and decided to have an anal Pap test following many years of HIV (human immunodeficiency virus) treatment and participation in a surveillance program. Despite having put off the screening for a few months, Ed knew that since he had HIV, he was at higher risk for HPV (human papillomavirus) and anal cancer.

The anal Pap test showed cells, which were concerning for cancer, and a subsequent biopsy of a suspicious-looking lesion proved to be cancerous. After additional studies, Ed was diagnosed with early stage anal cancer. The fortuitous discovery in October of last year allowed him to forgo surgery and, instead, receive six weeks of chemotherapy and radiation.

Although his treatment was challenging, the holidays and the month of January allowed Ed to rest and recover. In February, he felt good enough to return to work and subsequently began following a vegan diet, exercising regularly and better managing diabetes and stress. Due to the clarity that accompanied his hardship, Ed said he almost feels lucky to have gone through this experience because of everything it taught him — especially the importance of educating yourself, finding a good care team and learning to be his own best health advocate.

Anal cancer and HPV

Anal cancer occurs when skin cells grow out of control in the anus. The causes and location of anal cancer should not be confused with colon or rectal cancer, which are different.

According to the American Cancer Society, about 90 percent of anal cancers are caused by HPV. It is important to know that there are many strains or types of HPV and not all of them cause cancer. Most cancers of the cervix and anus are caused by HPV strains 16 and 18, while other HPV strains cause genital warts. HPV is the most common sexually transmitted disease and most people are exposed to HPV numerous times over their lifetime.

Thankfully, HPV infection usually goes away on its own. However, when the immune system is damaged by HIV and other causes, HPV infection can last longer and cause changes to the skin inside the anus, which is called “dysplasia.” Over time, some of these HPV-damaged cells – called “High-Grade Squamous Intraepithelial Lesions” or HSIL – can develop into cancer. Although HSIL is not the same as cancer, it is an indication that cancer may develop in that spot at a later date. Unfortunately, researchers do not currently know why some HSIL go away on their own while others worsen and become cancerous.

Who is at risk?

Anyone can get anal cancer, even people who have never had anal sex. However, it is much more common in people who are HIV-positive. For perspective, in HIV-negative people the chance of developing anal cancer is one to two people per 100,000. In HIV-positive people, it is between 30 and 131 per 100,000. (The rate in HIV-positive women is lower than in men.) In fact, even HIV-positive people on successful antiretroviral therapy have a higher risk of anal cancer than HIV-negative people.

Risk factors

The most common risk factors for anal cancer include:

  • Infection with certain strains of HPV
  • Age (risk increases with age)
  • Having a low count of T-helper cells, a type of white blood cell
  • Smoking
  • For women: a history of HPV-related cervical and vulvar dysplasia and/or cancers
  • History of genital warts


Early stages of anal cancer are often not accompanied by symptoms, which means most people are unaware when they begin to develop it. In later stages, the most common symptom reported is pain, which can be felt constantly or only when having a bowel movement or anal sex. Other symptoms can include a lump or bleeding from the anus. Unfortunately, anal cancer is often misdiagnosed as a hemorrhoid. If you are having any of these symptoms, it’s important to tell your doctor.


Like most types of malignancies, the earlier anal cancer is found and treated, the fewer side effects people face from treatment. When caught early, anal cancer usually responds well to treatment. Some small cancers can be removed surgically. However, once the cancer spreads, treatment may require a combination of chemotherapy, radiation and surgery. Removing the affected areas can “cure” anal cancer, but there are often long-term side effects from surgery, radiation and chemotherapy, like needing to go to the bathroom more often.

Research: Virginia Mason, Harborview and The Polyclinic in national screening study

Thankfully, deaths from AIDS are way down. However, anal cancer among people living with HIV is on the rise. Researchers think anal cancer can be prevented by routine screening and removal of precancerous cells. In fact, researchers at Virginia Mason, Harborview and The Polyclinic are participating in a national clinical trial called The ANCHOR Study (ANCHOR stands for “Anal Cancer HSIL Outcomes Research”). This strategy has reduced cervical cancer rates by 80 percent. But to get health insurance companies to cover routine anal cancer screening and preventive treatment, researchers need to prove this strategy prevents cancer.

The best way to demonstrate effective prevention is to recruit people with HSIL into a study, with groups assigned randomly to a treatment arm or a monitoring arm. Researchers will then follow everyone for five years to compare the rates of cancer in both study arms. At the end of the study, researchers will know whether screening and treatment of HSIL are effective strategies in preventing anal cancer. Researchers will also learn a lot about HPV and other risk factors and why these sometimes cause cancer.

If you have any questions about whether this study might be right for you, talk with your doctor and have your provider call a local study site with any questions. For more information about The ANCHOR Study, including the list of study sites and contact information, visit

Words of wisdom

Although Ed is not a candidate for participation in The ANCHOR Study, he now understands the importance of screening for anal cancer, especially among people living with HIV. Despite needing to come to Virginia Mason twice a year to be checked to make sure the cancer doesn’t grow back, Ed feels very thankful and encourages male and female friends who may be at risk to speak with their physicians about a Pap test. After all, knowledge is power.

David M. Aboulafia, MD, is board certified in Internal Medicine. His subspecialties include Medical Oncology, Hematology and HIV Clinical Care. Dr. Aboulafia is principal investigator of The ANCHOR Study at Virginia Mason and medical co-director of Bailey-Boushay House. He practices at Virginia Mason Hospital and the Floyd & Delores Jones Cancer Institute (1100 Ninth Ave, Seattle, WA 98101; 206-223-6193).

A version of this article previously appeared in the Seattle Gay News and the Queen Anne & Magnolia News.

Game Therapy Shows Promise for Treating “Lazy Eye” in Children

Hee-Jung Park, MD

Hee-Jung Park, MD

A common cause of decreased vision in children is amblyopia, also known as “lazy eye.” Often confused with strabismus, or the misalignment of the eyes, amblyopia refers to vision reduction in one eye due to the brain favoring the other eye. Any condition that affects normal eye function, including strabismus or problems with focus, can cause amblyopia. The longer one eye is suppressed, the greater the chance of permanent vision impairment.

Treatment for amblyopia in children frequently involves patching the good eye, forcing the use of the weaker eye. Disengaging the good eye does not, however, address the underlying cause of amblyopia: the loss of binocular function.

A promising new treatment option that helps the eyes work together has shown measurable improvement in participants’ binocular perception, visual acuity and depth perception in early studies. Known as binocular game therapy, the treatment involves a game played on an iPad. The player moves or rotates falling blocks on the screen to build rows of solid lines. By wearing special glasses during play, higher contrast images are presented to the amblyopic eye, while the normal eye sees lower contrast. The effect helps the player combine visual information from both eyes.

“Binocular game therapy is the biggest breakthrough we’ve had in the treatment of amblyopia in probably 50 years,” says Hee-Jung Park, MD, MPH, pediatric ophthalmologist.

Dr. Park is a participating physician in the Pediatric Eye Disease Investigator Group overseeing a new clinical trial to compare the effectiveness of game therapy versus eye-patching treatment. Funded by the National Eye Institute, the study will include more than 500 children across North America and Europe.

After a qualifying eye exam, study participants ages 5 to 16 years will be randomly assigned to binocular game therapy or eye patching. Vision and eye alignment will be checked throughout the study. All participants who receive the eye patching treatment during the 16 week study will be given the opportunity to try game therapy at no cost. Recruiting for the study is active now, concluding September 2017.

Complete clinical trial information for the Study of Binocular Computer Activities for Treatment of Amblyopia is available here. Virginia Mason Medical Center in Seattle is now a study site and provides qualifying eye exams for children by Dr. Park, performed in Seattle and Issaquah. To find out more about the clinical trial at Virginia Mason, please contact the clinical research coordinator at (206) 342-6598.

Food for Thought: A Current Look at Children’s Food Allergies

David Jeong, MD

Pediatric allergist David Jeong, MD, works with Benaroya Research Institute to explore the basic science of food allergies in children.

Whether or not we have a personal connection to food allergies, most of us are familiar with their impact. From peanut restrictions in schools to the prolific advertising of emergency auto-injectors, there’s a wider awareness of how severe food allergies can disrupt and even threaten lives.

It’s not our imagination that food allergies have spiked in recent years. According to a 2013 study by the Centers for Disease Control and Prevention, allergy rates in children increased approximately 50 percent between 1997 and 2011. What accounts for such a steep increase?

“First we must get away from the notion that just one thing causes food allergies,” says pediatric allergist David Jeong, MD. “The hygiene hypothesis, which points to excessive cleanliness skewing immune system development, may have some validity, but there’s a bigger picture. We see differences in food allergy rates by regions and cultural factors, such as the way food is prepared. For example, in the U.S. peanuts are often roasted which impacts how allergenic they are. Another difference among diverse populations is when foods are first given to children.”

Dr. Jeong notes that prior to 2008, the American Academy of Pediatrics recommended potentially allergenic foods – such as peanuts – not be given to children before three years of age. Yet studies of cultures that introduced peanuts earlier showed fewer food allergies than their peanut-delaying counterparts. Current guidelines now recommend delaying any solid food until four to six months of age, but there are no suggested delays for giving allergenic foods beyond six months.

Because food allergies can come on in infancy, Dr. Jeong recommends introducing one new food at a time in the first six to 12 months. That way a trigger food will be easier to identify. Even if it seems clear a certain food causes a reaction, it’s important to visit a pediatrician or allergist to have a test confirming the allergy.

As food allergies have no cure, avoidance of the trigger food remains the best defense, with antihistamines or epinephrine injectors on hand in case of accidental exposure. But promising new treatments are on the horizon, says Dr. Jeong, with some of the most advanced research and clinical trials happening right here in Seattle.

The Seattle Food Allergy Consortium (SeaFAC) is a collaboration of six institutions committed to world class food allergy treatment and research, and includes Virginia Mason, Benaroya Research Institute at Virginia Mason, Northwest Allergy and Asthma Center, UW Medicine, Seattle Children’s and  ASTHMA Inc Clinical Research Center.

“SeaFAC clinical trials are underway to discover if patients can be safely desensitized to food allergens, a type of immunotherapy,” says Dr. Jeong. “Immunotherapy has been around for many years in the form of allergy shots for environmental and bee venom allergies. In the future we may learn that controlled exposure to food allergens over time can reduce the severity or eliminate allergic reactions from foods.”

Dr. Jeong acknowledges some medical practices may be administering immunotherapy for food allergies “off-label,” but he cautions the treatment is still experimental and patients must understand the risks. Dr. Jeong suggests interested parents of children with a confirmed diagnosis of peanut, tree nut, milk, and/or egg allergy contact Benaroya Research Institute at Virginia Mason to learn about eligibility for clinical trials. Email, or call
(877) 202-5200. To explore more food allergy research, education and local community resources provided by SeaFAC, visit


Food Allergies Motivate Boys to Contribute to Research

Most kids take a backpack to school for their books and lunches. But since they were 4 and 7 years old, Aaron and Justin carry their backpacks everywhere. They are filled with lifesaving medications including epinephrine auto injectors and Benadryl. Aaron also carries an asthma inhaler.

The Newton boys both have peanut allergies. Living with a food allergy is different, says Justin, now 12. “You can’t eat everything and you have to look at labels to see if the food is safe. It’s harder to go out with friends because you can’t always eat everything.”

Aaron & Justin Newton with their lifesaving supplies for peanut allergies. They contribute to the Allergy & Asthma Biorepository“You have to be careful at every single restaurant,” says Aaron, now 9. “If I’m having a reaction, I need to call 911 and use my EpiPen.” He has twice experienced cross contamination reactions after eating food from restaurants. “That was scary because I couldn’t breathe.”

Their mother, Lori Newton, says that having kids with food allergies requires always being vigilant. “You must always be prepared by carrying medicines, knowing what food will be served, having good alternatives for foods and being hyperaware of your surroundings.

“It’s hard because we enjoy good and adventurous food at restaurants, but we always need to thoroughly check them out first. It’s also difficult when the kids can’t eat what the group is eating at a birthday party or banquet,” she explains. “The vast majority of people understand but some don’t and serve items that are not safe for my kids.”

BRI is a worldwide leader in investigating better ways to diagnose, treat and cure allergies. The Newton family is helping with this work. Justin and Aaron have joined the BRI Allergy and Asthma Biorepository, a list of people with allergies and asthma who are willing to donate a blood sample and provide health information to support scientific research. The information is used by scientists to better understand the causes and long-term health effects of allergies, asthma and immune mediated diseases, as well as to explore better treatment options.

Mary Farrington, MD, a Virginia Mason allergy specialist, informed them about the study. Justin now takes time out from his karate and running to give blood for the research. “I hope that this will be helpful for others and help me too,” he explains. “Maybe there will be a cure someday.” Aaron loves to play baseball and other sports, and hopes to help people with allergies too.

“We talk about the studies and how they help us learn more about their allergies,” says Lori. “It’s exciting to think that our experiences can help us and others so that kids won’t have to worry about not breathing from eating an allergen.” She has high hopes for allergy immunotherapies delivered by patches or orally. “Dr. Farrington believes that we can lead wonderful, productive lives despite our allergies. As my kids grow older, she is helping them take ownership of their care and action plans.”

bio-8-top-allergies-550wDid You Know?

  • Up to 15 million Americans have food allergies.
  • This potentially deadly disease affects 1 in every 13 children (under 18 years of age) in the U.S.
  • Allergies occur when the body’s immune system overreacts to a foreign substance (an allergen), such as food, pollen or animal dander, that in most people is generally harmless.
  • People react to the proteins in these allergens with an antibody that releases chemicals that cause sneezing; itching in the nose, eyes and ears; and in rare cases the life-threatening reaction anaphylaxis.

Learn more about the Allergies and Asthma Biorepository.


A version of this article first appeared in the BRI Newsletter.