Archive for the ‘Articles’ Category

Dr. Green’s research led to lymphoma breakthrough

by Kalani Simpson, UNMC public relations

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Michael Green, Ph.D., assistant professor in the Eppley Institute,
A new recruit to the Fred & Pamela Buffett Cancer Center begins his UNMC career on the heels of a major contribution to a breakthrough in Hodgkin’s lymphoma treatment.

Clinical trial results for the new therapy inspired by his research were detailed in a December 2014 edition of The New England Journal of Medicine.

Michael Green, Ph.D., assistant professor in the Eppley Institute, while a postdoc at Dana-Farber Cancer Institute in Boston in 2010, was first author on the discovery of a therapy target — a gene whose increased expression allowed cancer cells to evade being seen and eradicated by the immune system.

Expression of this gene may be why Hodgkin’s relapse rates can be as high as 25 percent.

“It’s a ligand on the tumor cell surface that binds to a receptor on the T-cell and tells them not to perform their normal function,” Dr. Green said. “Its natural role in biology is after an infection to try and bring down the immune response after the infection has been cleared. But it has been hijacked by these cancer cells so they can shut down an anti-tumor immune response.”

Thankfully, there was a potential neutralizing antibody already in clinical trials. So a study involving patients with relapsed or refractory lymphoma got to skip straight to Phase II, to “a pretty remarkable result,” Dr. Green said. The treatment was awarded breakthrough therapy (BT) designation by the FDA. Dr. Green had already left for Stanford University by the time the clinical trial started, but feels very satisfied with the end result.

“That’s why we do what we do,” he said. “Publications and grants are nice but this is the real reason behind our research.”

At Stanford, Dr. Green turned his attention to the as-yet incurable follicular lymphoma. And there is no better place to continue this research, he decided, than at UNMC, where Jim Armitage, M.D., and Julie Vose, M.D., head up a world-renowned lymphoma study group.

“That was imperative in coming here,” he said. “I’m doing a lot of next-generation sequencing and there’s a genomics core here. I do a lot of immunology and there’s a very good flow cytometry core here. And the biggest thing really is a massive bank of tumors here.”

And the relationship history with the patients who gave them.

Now, Dr. Green is studying a novel gene mutation which helps follicular lymphoma cells evade the immune system. “We have defined the mutation we want to target, so now we are trying to identify a specific therapy — it is a great example of ‘precision medicine.'”

New insights in lung cancer treatment

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APAR KISHOR GANTI, MD

In the past decade, we’ve come a long way in our knowledge of lung cancer. Until then, we had only a basic understanding of the tumor cells – and chemotherapy helped only a small percentage of patients.

We knew very little about lung cancer cells. We only knew about “small cell lung cancer” and “non-small cell lung cancer,” which basically was everything else. Today, from 10 to 15 percent of lung cancers are the small cell type.

We knew there were differences among these “non-small cell” cancers. But we didn’t have the tools to identify them, and we didn’t know how to treat them. Everyone got the same chemotherapy treatment, which was very effective in some cases – but not for many.

That changed when drug called Iressa was introduced in the U.S. This drug helped a small minority of patients – and they responded dramatically. Their tumors disappeared in a matter of weeks. Unbelievable!

This led to research to find out more about these patients. This also started a revolution in understanding different sub-types of non-small cell lung cancer. Today, using sophisticated tests, we can identify the main mutation causing lung cancer in a significant proportion of patients.

This research has led to targeted treatments we use today, with much greater success. New drugs have been developed to treat two of these lung cancer sub-types. These drugs primarily help people who have not been smokers – but have developed lung cancer from other toxic exposures, like radon.

Erlotinib, Afatinib, Pemetrexed, Crizotinib and Ceritinib are drugs that that we use today – to treat some of these specific types of lung cancer. Many of these drugs and others like these are still in clinical trials, to study their effectiveness. While we still don’t have all the answers, and still don’t have drug treatments that help everyone, we’ve come a very long way.

Several more medications are in clinical trials. We’re continually looking for more answers, trying to help many more lung cancer patients. But our progress in the past 10 years has given all lung cancer patients – and medical specialists like me – more hope.

At Nebraska Medicine, our service is designated by the National Cancer Center as a Lung Cancer Alliance Screening Center of Excellence. This reflects our team’s experience as well as our multidisciplinary program in managing patient care.

With this level of expertise, you will receive the treatment that specifically targets your lung cancer sub-type. We’ll stay with you every step of the way, making sure you’re getting excellent care.

Take heart that, when your cancer is caught at an early stage, you stand a very good chance of cure. The American Cancer Society reports that over 430,000 people alive today have been diagnosed with lung cancer at some point.

A Transplant’s Not the Only Alternative for Children With Intestinal Failure; Rehab is an Option for Most Patients

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DAVID F. MERCER, MD, PhD

Our intestinal transplant program has a worldwide reputation. We’ve performed more intestinal transplants here at The Nebraska Medical Center than any other single hospital in the world. We helped pioneer the procedure.

But whenever possible we prefer not to do it.

Rehab for our pediatric intestinal failure patients is so successful, we don’t need to transplant very often. Rehab has become our default – with transplant as a wonderful backup plan, but no longer the only option.

Our patients come from all over the country and around the world. Many times, parents have been told that an intestinal transplant is the only treatment for their child. But when they arrive, we start with what they have – whatever the child’s condition and function – and go from there. It’s better to build on whatever they have than to start over. The family goes from having no hope to realizing that, very likely, their child will be able to live and eat normally.

When a child comes to our program, the family needs to be here four to six weeks. That sounds like a long time at first. But once they arrive, the families are so relieved and comfortable, often they don’t want to leave. Regardless of when they return home, they are part of the program for life.

Here’s what usually happens. The first week is evaluation with testing every day, and we make a plan. Next is an inpatient stay for a surgical intervention. Then it’s outpatient care for the next few weeks, attending weekly clinics and communicating almost daily with our team as we work on improving function in the intestinal tract, finding a pathway that will work for them and carefully moving toward our goal of eating and drinking by mouth.

When I tell parents that we hope their baby will one day go to kindergarten, carry a lunchbox to school and eat just like other kids, it blows their minds. But that is the goal, and we see our patients reach it all the time. It takes time and a dedicated team of experts guiding the way, but we get there working together. The family has been told to expect the worst; we let them know to expect the best.

There are times when we meet a child and we decide that the risks of taking time to work on intestinal rehabilitation are too high – that perhaps there has been too much damage done prior to their arrival.  There are other times when, despite everything we do, we cannot make progress and the risks of being on TPN begin to mount. These are the times when we turn to transplant, and in these cases it is truly lifesaving.

Rehabilitation and transplantation aren’t competitors with each other, but rather they work together so the right thing can be done for a child at the right time. When we can, we always prefer rehab, because successful intestinal rehabilitation doesn’t just delay the need for a transplant – it eliminates it.  When that goal can’t be achieved, transplant moves in to provide lifesaving therapy.

With these two complementary tools, the child with intestinal failure has a great chance to live a full, productive life.

NICU Team Saves Baby Diagnosed With Rare Condition

Genevieve was born with a rare condition called congenital chylothorax. She was hydroptic, collecting fluid in her body tissues and around her lungs.

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Genevieve was born with a rare condition called congenital chylothorax.

“The miracle on 42nd Street,” is how Genevieve Wright’s family describes their strong, resilient little girl.

On February 19th, Genevieve was born at Nebraska Medicine – Nebraska Medical Center with a rare condition called severe congenital chylothorax. She was hydroptic, collecting fluid in her body tissues and around her lungs. Only two percent of babies born with this condition survive. Most die inside the womb, or moments after birth.

“We’ve done a lot of crying and praying,” says Genevieve’s mom, Shelly Wright. “Genevieve has been in the fight of her life.”

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Shelly Wright enjoys cuddling with her 2-month-old daughter, Genevieve.

Over the last two months, Ann Anderson-Berry, MD, medical director of the NICU, inserted 14 chest tubes to drain the fluids from Genevieve’s body. Some days, the NICU team removed three cups of fluid. They also worked to replenish blood and electrolytes that Genevieve was losing. Dr. Anderson-Berry says, Genevieve’s case is unlike any other documented. There were no case reports that outlined a successful treatment plan. Most days, the NICU team wasn’t sure she’d survive.

“It’s been minute to minute,” says Dr. Anderson-Berry. “But, if you look at her now, you’d never know she was so critical. Genevieve is writing her own story.”

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Dr. Ann Anderson-Berry, medical director of the NICU at Nebraska Medicine, speaks with local reporters about Genevieve’s condition.

This week, Genevieve will likely be discharged and go home to join her parents and three siblings in Lincoln, Neb. She’s off the ventilator and respiratory support. She’s acting like a normal newborn, smacking her lips, smiling and scanning the room with her eyes.

“I feel like all I do is stare at her,” says Wright. “Where there’s life, there’s hope. This medical team really gave it their all. You gotta give them a chance, even the two percenters.”

Collaboration impacts personalized cancer treatment

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Babu Guda, Ph.D., associate professor and director of the Bioinformatics Systems Biology Core Facility at UNMC

The Fred & Pamela Buffett Cancer Center has partnered with IBM to conduct early testing and feedback for IBM’s Watson Genomic Analytics program.

The IBM program in minutes identifies relevant mutations and potential drugs that may be considered in a treatment regime — all based on the patient’s genomic profile and the specific mutations.

The Fred & Pamela Buffett Cancer Center at UNMC and Nebraska Medicine in Omaha, is one of 14 leading cancer institutes to partner on the project, which is part of IBM’s broader Watson Health initiative to advance patient-centered care and improve health while building on IBM research advancements.

Most of the 1.6 million Americans who are diagnosed with cancer each year receive standard treatment. When standard treatment fails and with genetic sequencing becoming increasingly accessible and affordable, some patients are beginning to benefit from treatments that target their specific cancer-causing genetic mutations.

Babu Guda, Ph.D., associate professor and director of the Bioinformatics Systems Biology Core Facility at UNMC, will be collaborating with Ken Cowan, M.D., Ph.D., director of the Fred & Pamela Buffett Cancer Center and breast cancer physician, to analyze cancer tumor genomes on the project.

“IBM has fed millions of research articles into the program, including biomedical research and clinical information,” Dr. Guda said. “The cognitive computer can keep track of the complex relationships among gene mutations, drug treatments and treatment outcomes.”

IBM describes cognitive computing as computers that learn and interact naturally with people to extend what either humans or machines could do on their own to help human experts make better decisions.

With each patient, the cancer center team is sequencing the genomes of normal and tumor tissues and identifying variations that are specific to the tumor tissues. Tumors can have many mutations, but some — “driver mutations” — are critical for the initiation and progression of cancer.

“Typically, we get several thousands (of variations),” Dr. Guda said. “Not every change is important, but some driver mutations or other serious mutations that alter cellular function may give a selective advantage for cancer cells to proliferate and spread the disease to distant locations,” he said.

Steve Harvey, vice president, IBM Watson Health, said Watson will help deliver personalized cancer care using the latest advances in science by integrating complex and disparate data in a cognitive system. “Ultimately, our goal is to create a solution that any oncologist in any location can use to identify personalized treatment options for their patients.”

Dr. Are is UNMC’s OTICA winner

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Chandra Are, M.B.B.S.

Chandra Are, M.B.B.S., vice chair of education for the UNMC Department of Surgery, associate professor of surgical oncology, and program director for general surgery residency at UNMC, is a recipient the University of Nebraska’s Outstanding Teaching and Instructional Creativity Award (OTICA).

Chancellor to speak

UNMC Chancellor Jeffrey P. Gold, M.D., will give his annual address to the faculty at 4 p.m. on Thursday in the Durham Research Center Auditorium as part of the annual faculty meeting. Faculty Senate President Gay Canaris, M.D., assistant professor, internal medicine, College of Medicine, will provide an overview of the year’s activities. Following the address and the award presentations, Dr. Gold will host a reception in the center’s foyer.

Awards will be presented for Outstanding Teacher, Spirit of Community Service, Outstanding Faculty Mentor of Graduate Students and Outstanding Mentor of Junior Faculty, as well as the University of Nebraska’s Outstanding Teaching and Instructional Creativity Award (OTICA) and Outstanding Research and Creative Activity (ORCA) Award. Faculty members also will be recognized for their 5, 10, 20, 30 and 40 years of service.

Since arriving at UNMC in 2007, Dr. Are has earned a reputation as an innovative educator, a meticulous surgeon, and someone with exemplary dedication to patients.

His innovative thinking led to the establishment of an international rotation program that allows residents to spend nearly six months in India, expanding their international awareness and exposing them to different health care models.

Dr. Are also was instrumental in the development of a novel surgical anatomy curriculum for first-year medical students, physician assistant and physical therapy students. Similarly, he developed an innovative and unique open surgical skills/procedures training curriculum for general surgery residents using lightly embalmed cadavers.

Since simulation is at the forefront of medical school education, Dr. Are’s efforts to stay ahead of the curve led to a virtual simulation-based operating room in the Sorrell Center.

Finally, to help residents pass their American Board of Surgery In-Training Examination (ABSITE) exit exams and improve their scores, Dr. Are developed a remedial course.

Dr. Are’s impact is best summed up by his students, with one former student calling Dr. Are “the most influential person” during his general surgery training.

Asked about his teaching philosophy, Dr. Are said it was to “teach unto others what has been taught to you with respect, and to train students not only to acquire competence but also build good character.”

10/10 Finding Balance

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The pain that Rachel Smith felt just under her breastbone was like no pain she had ever felt before. It was debilitating pain; pain that caused her to drop to the floor unable to stand pain. On a scale of one to 10, it was a 10.

That’s how Smith remembers her first pancreatitis attack. It landed her in the hospital for six days.

Doctors diagnosed her with acute pancreatitis and sent her home on a liquid diet, pain medications and instructions to eliminate all alcohol consumption.

 

Story_Vertical_Balance2RACHEL SMITH

But the pain continued. One week later, Smith was back in the hospital for eight days, then two weeks later for nine days and then another two weeks later for two weeks. During this last visit, she was put on a feeding tube. She was not allowed to eat or drink anything as doctors tried to determine the source of her pain. Her doctors were stumped. They tried more pain medications. One suggested removing her gallbladder. But even more frustrating, no one seemed to listen or take the 22 year old seriously. It was a frightening and frustrating time, Smith says.

Everything changed, however, when a friend of Smith’s mother suggested she visit The Nebraska Medical Center’s Comprehensive Pancreatobiliary Disorder and Autologous Islet Transplantation Clinic. The only clinic of its type in the region, the clinic specializes in non-malignant pancreatic and biliary diseases and offers a full array of diagnostic and therapeutic modalities. The most common conditions the clinic treats include benign neoplasms of the pancreas as well as acute and chronic pancreatitis.

A Standing Ovation

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Cora Christensen describes her care at The Nebraska Medical Center like that of a well-rehearsed symphony — a welcome relief when much of her health over the past 30 years has been more like an opera with its share of tragic moments.

Having the right care in competent and experienced hands not only saved her life but has given her a sense of peace and harmony. “It’s so much more fun being alive now that I know I have a team of doctors who can take care of me if something goes wrong,” says the 60-year-old Christensen. “I’m not scared anymore.”

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Curtis Hartman, MD

Scene 1 of Christensen’s story begins at age 33 when she was diagnosed with familial cardiomyopathy. A condition characterized by thickening of the heart muscle, this can impede blood flow and worsen with age, leading to a host of problems including arrhythmia, shortness of breath, dizziness, fatigue and heart failure. For some 15 years, Christensen treated the condition with medications.

By the time Christensen had reached her late 40s, the drama began to unfold. She started to experience fatigue, occasional dizziness and arrhythmia. The arrhythmias became more frequent and, at age 53, Christensen underwent surgery to have an implantable cardioverter defibrillator (ICD), a device that continuously monitors your heart. If it detects a life-threatening rapid heart rhythm, it sends an electric shock to your heart to restore a normal rhythm. Although the ICD did its job, saving Christensen from serious arrhythmias in numerous instances, Christensen’s condition continued to worsen.

The arrhythmias became more severe and bouts of dizziness, shortness of breath and fainting spells made it difficult to work. A teacher at Metropolitan Community College, she eventually had to quit. At the same time, Christensen was also going to school to get her master’s degree, a goal she refused to give up on.

Then she had a heart attack. Subsequent tests showed her heart was barely functioning. Her doctors sent her to The Nebraska Medical Center’s Heart Failure Clinic where she was diagnosed with end-of-life-cardiac failure. “I was barely cognitive,” recalls Christensen. “They said my ejection fraction was only 7 percent.”

Keeping Hope Alive | Personalized Brain Cancer Treatment

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No one wants to hear the word cancer. But if there is one cancer that you would least like to hear come from your doctor’s mouth, it would probably be brain cancer.

While brain cancer is very rare, affecting less than 1 percent of the population, it also has one of the least favorable outcomes.

Craig Harrison, RN, is very familiar with these facts. Not only is he a nurse, but he often cares for brain cancer patients on the neuro intensive care unit at The Nebraska Medical Center.

Story_Vertical_HarrisonCraig Harrison

 

In 2012, when Harrison was just 26 years old, brain cancer became a very intimate part of his life.

Harrison was working in the neuro intensive care unit at The Nebraska Medical Center, doing a little home remodeling on the side and playing golf in his free time. He was planning to go back to school to become a nurse anesthetist and had dreams of having a family of his own and traveling the world. At 26 years old, life was carefree and full of hope.

On a beautiful fall day in September 2012 Harrison met his friends to play golf. The game came to an abrupt end, however, when at the par 3, 2nd hole, Harrison felt a strange sensation pass through his body before falling to the ground.

“All I remember from that point was trying to tell my friends that something wasn’t right, but I was unable to speak to them and unable to move,” recalls Harrison. “The last thing I remember is falling over, and then waking up on my back looking at the bright blue sky above and hearing peoples’ voices telling me that I had had a seizure.”

His friends called 911 and Harrison was taken to The Nebraska Medical Center. After undergoing a series of tests, doctors determined that Harrison had suffered a seizure that they suspected may have been triggered by a primary brain tumor — difficult news to swallow for a 26 year old with a full life ahead of him.

Fear initially engulfed him, Harrison says. But that eventually subsided when he met neuro-oncologist Nicole Shonka, MD, who would lead his treatment and care plan. “I was very comfortable with her from the first time we met and confident in her care,” he says. “She immediately put me at ease and I weighed her advice very heavily in my decisions.”

Grant will help lab’s efforts to battle ovarian cancer

by John Keenan, UNMC public relations

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Cheng Wang, Ph.D.

Cheng Wang, Ph.D., assistant professor, obstetrics/gynecology, recently received a grant to study the initiation and progression of ovarian cancer.

The $70,000 grant came from Colleen’s Dream Foundation and local community efforts in Harlan, Iowa.

About the Foundation

Colleen’s Dream Foundation started in 2012 and supports research for early detection and improved treatment for ovarian cancer. Based in Phoenix, the foundation is named after Colleen Drury, who died of ovarian cancer after a five-year battle. NFL kicker Billy Cundiff, a member of the board of directors and Colleen’s son-in-law, is a former Harlan Cyclone. For more information on the foundation board, click here.

Dr. Wang, in collaboration with Jixin Dong, Ph.D., of the Fred and Pamela Buffett Cancer Center, is investigating whether the hippo signaling pathway drives migration and proliferation of the cancer cells. His studies show that a recently-described new cell signaling pathway which controls organ size and how rapidly cells divide, may be responsible.

“The disruption of the Hippo pathway transformed these cells,” he said.

Suppressing the Hippo pathway, or overexpression of the YAP pathway, can lead to organ overgrowth or tumor growth. But whether the pathway contributes to the initiation of ovarian cancer cells is currently unknown.

In addition, Dr. Wang will be investigating whether, as some recent studies have conjectured, the Fallopian tube is the primary site of origin for ovarian cancer.

“This is important, because it was previously believed ovarian cancer came from ovarian surface epithelial cells (OSE), and it possibly may originate from fallopian tube secretory epithelial cells (FTSEC),” Dr. Wang said.

Still, there is no direct evidence, for now. Dr. Wang’s project also may provide molecular evidence to show that ovarian high-grade serous carcinoma originates in the fallopian tubes.

“This has important clinical implications,” Dr. Wang said. “Early cancer screening tests may allow surgical removal of malignant cells, preventing them from colonizing ovarian tissue.”

“Understanding how the tubal cells colonize the ovary may facilitate the development of methods to prevent cancer cells invading the ovary.”

The implications are especially important because despite the rapid progress made in ovarian cancer research in the past several decades, the mortality rate of patients with ovarian cancer remains very high. It is the most lethal female cancer in the U.S. In 2014 alone, the American Cancer Society estimates that 21,980 new cases will be diagnosed.

“If the diagnosis is made early, 90 percent of the women are saved,” Dr. Wang said. “With a later diagnosis, the survival rate is less that 40 percent, and at stage four, it’s 10 to 20 percent. Early detection is very important.”

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