UPMC Physician Resources

Experimental Radioprotective Drug Safe for Lung Cancer Patients, Says University of Pittsburgh Cancer Institute Study

PITTSBURGH, March 22, 2011 – Patients with advanced non-small cell lung cancer can safely take an experimental oral drug intended to protect healthy tissue from the effects of radiation, according to a study led by researchers at the University of Pittsburgh Cancer Institute (UPCI) and published in this month’s issue of Human Gene Therapy.

The findings support further clinical testing of the agent, called manganese superoxide dismutase (MnSOD) plasmid liposome, to determine if giving it alongside chemotherapy and radiation will prevent damage to normal cells that is the typical cause of side effects in cancer treatment, said senior investigator Joel S. Greenberger, M.D., professor and chair, Department of Radiation Oncology, Pitt School of Medicine, and co-director of the lung and esophageal cancer program at UPCI.

“If we can sufficiently protect tissues that are normal, we should be able to deliver our cancer treatments more effectively and perhaps even at higher doses,” he explained. “Our aim is to improve the quality of life of patients by minimizing side effects while providing the best treatment for their cancers.”

For the safety study, 10 patients with inoperable stage III non-small cell lung cancer took oral doses of MnSOD plasmid liposome twice weekly for a total of 14 doses during seven weeks of conventional chemotherapy and radiation treatment. The agent, which boosts levels of an antioxidant the body makes naturally, is made of fat droplets containing the gene that produces MnSOD. When swallowed, it is absorbed by cells in the esophagus, which is a common site for severe side effects during radiation treatment for lung cancer.

One patient experienced mild heartburn and a slight rash and another had mild constipation and a fluctuation in blood sodium, problems that might be associated with MnSOD treatment. No other toxicities were thought to be due to the experimental drug.

“The results of this initial trial indicate that MnSOD plasmid liposome can be safely administered,” Dr. Greenberger said. “It did not linger in normal cells after treatment, nor did it protect cancer cells from radiation treatment. The next study, which is underway at UPCI, is to determine whether it protects normal tissue, particularly the esophagus, from radiation exposure.”

A common toxicity of lung cancer radiation therapy is esophagitis, or inflammation of the esophagus, he explained. Within a few weeks of treatment, patients typically experience painful swallowing that over time can become so severe that narcotics or a break from radiotherapy may be necessary for patient comfort.

Preclinical testing has shown that generating higher levels of MnSOD in healthy cells can suppress the production of inflammatory molecules and reduce cell death, micro-ulceration and esophagitis. Because the agent is delivered to healthy tissue, it does not protect tumor cells from radiation treatment. In fact, Dr. Greenberger noted, experiments hint that when it is given to cancer cells, it actually encourages cell death because of abnormalities in their cellular metabolism.

He and his team plan to investigate the use of MnSOD plasmid liposome for other cancers, such as protecting the rectum from radiotherapy for prostate cancer and protecting the bladder during ovarian or endometrial cancer treatment.

The research team includes co-lead author Ahmad A. Tarhini, M.D., James D. Luketich, M.D., and others from UPCI; co-lead author Chandra P. Belani, M.D., of Penn State Hershey Cancer Institute; and others from Emory University, University of Washington School of Medicine, and PharmaReg Consultants, of San Leandro, Calif.

The study was funded by the UPCI Specialized Program of Research Excellence (SPORE) in lung cancer.

UPMC Uses New Technology to Treat Aortic Heart Valve Disease without Open Heart Surgery

PITTSBURGH, March 22, 2011 – UPMC has performed its first patient implants in the Medtronic CoreValve® U.S. Clinical Trial to evaluate a non-surgical, less-invasive procedure as a treatment alternative to open-heart surgery for patients who suffer from a serious narrowing of the heart’s aortic valve.

UPMC is one of 40 hospitals across the U.S. to participate in the trial for patients with severe aortic stenosis, which prevents the heart’s aortic valve from opening completely and in turn hampers healthy blood flow from the aorta to the rest of the body. Untreated, it can lead to serious heart problems.

A 66-year-old man, from New Alexandria, Pa., was one of the first patients at UPMC to receive the CoreValve implant. He suffered shortness of breath, which worsened when climbing stairs, and required oxygen nearly around-the-clock because of his aortic stenosis.

In January, physicians channeled a catheter through a small opening in his femoral artery to reach the heart. The physician then guided the CoreValve System to the aortic valve, where the valve self-expanded to replace the diseased aortic valve; the procedure was completed without open-heart surgery or surgical removal of the aortic valve.

“Now I’m practically not using oxygen at all,” the patient said.

His procedure was performed by William Anderson, M.D., director of Interventional Cardiology at UPMC, and Thomas Gleason, M.D., director of the Center for Thoracic Aortic Disease of the UPMC Department of Cardiothoracic Surgery.

“Aortic stenosis frequently occurs in elderly patients who have a higher risk of complications from standard valve-replacement surgery. This growing patient population may then have the most to gain from new, less invasive, catheter-based approaches to the implantation of a new aortic valve. The trial will allow us to explore this possibility,” Dr. Anderson said.

Worldwide, approximately 300,000 people have been diagnosed with this condition (100,000 in the U.S.), and approximately one-third of these patients are deemed at too high a risk for open-heart surgery, the only therapy with significant clinical effect that currently is available in the United States.

“Because open-heart surgery is currently the only available treatment option for these patients, and because the risks of surgery can be significant for many patients, the medical community is enthusiastic about the less-invasive option,” Dr. Gleason said.

In the U.S., the CoreValve System will not be commercially available until the successful completion of this clinical trial and approval by the U.S. Food and Drug Administration. The CoreValve System received CE (Conformité Européenne) Mark in Europe in 2007.

For more information about the Medtronic CoreValve U.S. Clinical Trial, visit www.aorticstenosistrial.com.

Physicians are available for interviews to discuss the clinical trial. Broadcast quality animation also is available.

Information about the clinical trial is available at www.clinicaltrials.gov.

Children’s Hospital of Pittsburgh of UPMC Receives Official LEED Certification

PITTSBURGH, March 17, 2011 Children’s Hospital of Pittsburgh of UPMC has become one of the first LEED®-certified pediatric hospital campuses in the United States.

On the Children’s campus, the hospital and mid-campus parking garage recently received official LEED (Leadership in Energy and Environmental Design) certification, which was established by the U.S. Green Building Council (USGBC) and verified by the Green Building Certification Institute. Children’s Hospital’s John G. Rangos Sr. Research Center has received LEED Silver certification, the third-highest designation attainable.

The new Children’s Hospital campus, located on 10 acres in the Lawrenceville neighborhood of Pittsburgh, opened in May 2009 and includes more than 1.5 million square feet of usable space.

“We’re proud to receive our official certification because it means we’ve achieved our goal of designing and building a world-class pediatric hospital that also is an extremely healthy, transformative and environmentally sustainable environment for our patients and families, staff and community,” said Eric Hess, vice president, operations, who also served as project executive for the new Lawrenceville campus. “From the early design stages, Children’s Hospital planned to develop a green campus that would meet the criteria for LEED certification. Even more impressive than being one of the first hospitals to achieve this status is the fact that we achieved this certification on two buildings, which comprise more than 80 percent of the total campus square footage.”

Children’s received LEED certification for energy use, lighting, water and material use, as well as for incorporating a variety of other sustainable strategies. By using less energy and water, LEED-certified buildings save money for families, businesses and taxpayers; reduce greenhouse gas emissions; and contribute to a healthier environment for employees, residents and the larger community, according to the USGBC.

Children’s commitment to employ green practices extends well beyond its bricks and mortar to operating policies and procedures regarding facility maintenance, housekeeping, food service and waste management. Children’s also fosters its green philosophy by working with clinicians, academicians and the community to conduct research on the subject of sustainability and its health effects on children. Additional environmentally sustainable initiatives include:

  • water-efficient landscaping with drip irrigation systems
  • use of building materials with recycled content (including recycled post-consumer structural steel)
  • use of regional construction materials to reduce transportation issues
  • use of low VOC materials such as sealants, adhesives, paints and carpets
  • installation of air filtration systems that increase indoor air quality
  • installation of water fixtures that reduce water use
  • maximum use of daylight and views and automatic shade systems to reduce cooling costs
  • access to a rooftop healing garden
  • continued use of recycled content and local materials whenever possible
  • access to public transportation
  • availability of bike racks and showers
  • employing a “green” education program for staff, patients and guests
  • utilization of 9.2 percent renewable electricity generation
  • energy optimization systems and heating and cooling recovery systems
  • plant materials with low water needs
  • fragrance-free cleaning products in most locations
  • low mercury lighting and no mercury equipment in the health care environment
  • waste reduction including recycling of batteries, paper, cardboard and kitchen grease
  • utilization of reusable sharps containers to minimize medical waste
  • development of a continuing medical education-accredited lecture series for residents that focuses on environmental health issues
  • implementation of a paperless information management system that allows physicians to place nearly all inpatient care orders electronically, eliminating handwritten and verbal orders

“Children’s Hospital’s LEED certification demonstrates tremendous green building leadership,” said Rick Fedrizzi, president, CEO, and founding chair, USGBC. “The urgency of our mission has challenged the industry to move faster and reach further than ever before, and Children’s Hospital serves as a prime example of just how much we can accomplish.”

Follow this hyperlink for more information about the new Children’s Hospital campus.

UPMC Presbyterian Shadyside President and UPMC Kidney Specialist to be Honored by National Kidney Foundation

PITTSBURGH, March 9, 2011 - UPMC Presbyterian Shadyside President John Innocenti has been named this year’s Corporate Gift of Life Awardee and Thomas Kleyman, M.D., chief of the University of Pittsburgh Renal-Electrolyte Division, has been named Medical Gift of Life Awardee by the National Kidney Foundation (NKF) Serving the Alleghenies.

Innocenti and Dr. Kleyman will receive their awards at the foundation’s annual Kidney Gift of Life Gala on Saturday, March 19 at the Circuit Center & Ballroom on the South Side.  “With World Kidney Day on March 10, we are honored to have outstanding individuals as our Gift of Life Awardees,” said Kevin Ho, M.D., a nephrologist at UPMC and the event chair.

“In addition to Mr. Innocenti’s leadership within the UPMC hospital system, he served as our NKF Corporate Walk Chairman in 2009 and 2010, making public appearances and attracting both sponsorship and contributions,” Dr. Ho said.

Dr. Kleyman is being honored for his contributions to kidney research. Dr. Kleyman is the director of the Pittsburgh Center for Kidney Research.

“Dr. Kleyman has contributed to our general understanding of how the kidneys process sodium and continues to advance nephrology research on multiple fronts,” Dr. Ho said.

Fertility Preservation Program in Pittsburgh Offers New Options to Even the Youngest Cancer Patients

PITTSBURGH, March 7, 2011 – One of the nation’s first comprehensive programs to help preserve or restore fertility after cancer treatment for not only adults, but also preadolescent girls and boys, has been established by a network of experts in reproductive medicine and cancer at Magee-Womens Research Institute (MWRI), Children’s Hospital of Pittsburgh of UPMC, Magee-Womens Hospital of UPMC and the University of Pittsburgh School of Medicine.

The Fertility Preservation Program in Pittsburgh aims to educate patients and their physicians about the long-term reproductive impact of cancer therapies and the options for preserving fertility ­­– some investigative – that are available to them, explained Kyle Orwig, Ph.D., associate professor of obstetrics, gynecology and reproductive sciences at the School of Medicine, an MWRI  researcher and one of the program leaders.

Studies show that up to 90 percent of cancer patients are not informed about the risks cancer treatment can pose to fertility, a statistic that physicians and researchers in Pittsburgh hope to change by offering counseling and services seamlessly coordinated with patient care.

“This is a discussion that needs to happen before toxic therapies are initiated and fertility is irreversibly destroyed,” said Dr. Orwig.

While adult men and women can freeze eggs, sperm or embryos prior to treatment, there currently are no options to preserve the fertility of boys and girls who are not yet producing mature eggs or sperm. “For these young patients, we will freeze testicular or ovarian tissue that might be used in the future to restore fertility when experimental techniques emerge from the research pipeline,” said Dr. Orwig. “In conjunction with pediatric oncologists at Children’s Hospital and the Center for Fertility and Reproductive Endocrinology at Magee, we are poised to provide standard as well as experimental options for preserving fertility.”

Surviving cancer is much more likely than it has been in the past, but patients who hope to eventually have biological children might face a new set of challenges because some treatments, particularly bone marrow transplant, can impair or destroy natural fertility.

“Many chemotherapies and radiation therapies work by killing rapidly dividing cells, which includes both cancer cells and innocent bystanders, such as the gonadal cells that make eggs and sperm,” Dr. Orwig said. “For example, leukemia could be treated with drugs to destroy the blood system, which is then restored with a bone marrow transplant. The cancer will be eradicated, but there is a significant risk that fertility will be wiped out, too, as a side effect.”

Preserving Fertility in Males

In the Fertility Preservation Program, Dr. Orwig and his team will cryopreserve, or freeze, testicular tissue from prepubescent boys with the hope that special precursor cells called spermatogonial stem cells can be obtained from it and later be given back to the patient in an “auto-transplant” that will allow sperm production to resume after cancer treatment.

While scientists can’t yet say for certain that collecting, storing and putting back spermatogonial stem cells will make it possible for boys to grow up to father children, the technique does appear to work in extensive animal testing, Dr. Orwig said.

An outpatient surgical procedure through the scrotum is necessary to collect testicular tissue. Ideally, it will be done when a cancer patient is already sedated in the operating room to get a central line, which is a long-term catheter placed in a large blood vessel for the administration of drugs and to draw blood for tests.

A small portion of the testicular tissue would be used for research, although if a sample is very small, all of it would be saved for the patient’s future use. Dr. Orwig’s team has already established techniques to determine whether stem cells are present and how many there are.

“One focus of our research is to isolate the therapeutic stem cells and remove contaminating malignant cells, so we don’t run the risk of reintroducing cancer when cells are given back to the patient,” he said. Spermatogonial stem cell transplantation is still a work in progress.  However, “a patient treated today who doesn’t cryopreserve his tissue will not be able to take advantage of this new technology when it becomes available,” Dr. Orwig added. “We are encouraged by successes in several animal models and believe this technique can be translated to the fertility clinic, possibly in the next decade.”

Men and boys who have gone through puberty could provide a semen sample that could be preserved for later use in an artificial insemination procedure, a simple and well-tested approach that would likely be the first choice for many male patients, Dr. Orwig said. But in some cases, the patient may be too ill from his cancer to provide a good quality sample, or he or his family may be uncomfortable with the act of producing one. Preservation of spermatogonial stem cells might be an option in such situations.

Preserving Fertility in Females

The Fertility Preservation Program also will endeavor to aid women and girls who are starting cancer treatment or preparing for a bone marrow transplant. Currently their choices are quite limited and, for many, biologically impossible or morally unacceptable, noted Joseph S. Sanfilippo, M.D., director of the Center for Fertility and Reproductive Endocrinology at Magee-Womens Hospital.

“Women can undergo ovarian stimulation to generate multiple mature eggs, which can then be fertilized with partner or donor sperm to produce embryos for later implantation and possible pregnancy,” he said. “These techniques are now well-established, and we will offer them to female patients who wish to pursue this option.” Another option is ovarian cryopreservation, where an ovary is removed before cancer therapy is initiated with the plan to replace ovarian tissue once the patient is cured.

Still, the stimulation technique takes time and could delay cancer treatment. It also produces high estrogen levels that could make some hormone-sensitive tumors worse, he noted. A component of the Fertility Preservation Program is to help individual patients understand the relevant issues to assist with decision-making.

For pre-adolescent girls, who don’t yet make eggs for fertilization, embryo freezing is not possible, said Peter Shaw, M.D., head of the Adolescent and Young Adult Oncology Program at Children’s Hospital and leader of the female side of the fertility preservation effort. He and his colleagues are working with National Physicians Cooperative of the Oncofertility Consortium, based at Northwestern University, to explore cryopreservation of mature eggs or ovarian tissue and other approaches to restore fertility after cancer.

Through the program, girls who have cancer and are at risk of losing their future fertility can have tissue samples stored. Conservative surgeries and other techniques can be used to try to preserve the reproductive system. Meanwhile, researchers around the country are trying to understand how the egg maturation process works to see if it is possible to rescue eggs or ovaries.

“We didn’t know until 33 years ago that a so-called ‘test tube baby’ was possible, so it’s very possible that we can find solutions for these problems in the near future,” Dr. Shaw said. “We have to try to preserve the tissue now or we will never succeed. We think the technology will be available in the future to use this frozen tissue to restore lost fertility.” Almost all of these options are experimental procedures, he acknowledged.

“We’re suggesting patients undergo an extra procedure while providing no guarantee that we can provide any help,” he said. “As always, it’s ultimately up to the patient and family. The most important thing we can do is provide them up-to-date information and resources.”

The Fertility Preservation Program has established a dedicated phone line that patients and their physicians can call to learn about the reproductive side effects of their treatments and options for preserving fertility.  The number is (412) 641-7475.

Drs. Ron Shapiro and Henkie Tan lead UPMC’s first participation in a kidney chain

Pittsburgh, PA, March 5, 2011–Rita Dolezal’s decision to donate a kidney to a complete stranger didn’t require a long discussion with loved ones.

“We never really spoke about it,” said Dolezal, 59, of Latrobe.

Two of the first people she told were her daughter, Diana, and her son-in-law, Troy Johnson, who had recently learned he needed a kidney transplant. Dolezal wasn’t a match, but her decision led to him finding a donor.

Through UPMC, the two participated in the largest kidney donation chain involving patients from Western Pennsylvania. By the time it ended last week, 32 operations had occurred in 12 states.

UPMC Participates In Kidney Transplant Chain

PITTSBURGH (KDKA), March 4, 2011 — About a year ago, Allegheny General Hospital was part of a large kidney chain, involving 12 transplants and 24 patients. Now, UPMC has surpassed that with an even bigger organ exchange involving 16 transplants, 32 surgeries, 12 medical centers and 10 states.

Read the full CBS Pittsburgh article, including photos and video:

http://pittsburgh.cbslocal.com/2011/03/04/upmc-participates-in-kidney-transplant-chain/

 

Pitt School of Nursing Study Finds Poor Sleep Quality Associated With Greater Pain And Disability In Rheumatoid Arthritis Patients

PITTSBURGH, Feb. 22, 2011 – Poor sleep quality correlated with higher levels of depressive symptoms, more severe pain, increased fatigue and greater functional disability in patients with Rheumatoid Arthritis (RA), according to a study by researchers at the University of Pittsburgh School of Nursing recently published in the Journal of Clinical Sleep Medicine. The study suggests that addressing sleep problems may have a critical impact on the health and quality of life of patients with RA.

Faith S. Luyster, Ph.D., assistant professor, School of Nursing, led the study of 162 patients with RA. Participants completed several questionnaires, which asked about their sleep quality, depression, fatigue, functional disability and pain severity.

Results showed that sleep quality had an indirect effect on functional disability after controlling for age, gender and number of comorbidities. According to results of one of the questionnaires, the Pittsburgh Sleep Quality Index, 61 percent of patients were poor sleepers and 33 percent reported pain that disturbed their sleep three or more times per week.

“Not sleeping well at night can contribute to greater pain sensitivity and fatigue during the day, which in turn can limit a patient’s ability to engage in activities of daily living and discretionary activities,” Dr. Luyster said. “These results highlight the importance of addressing sleep complaints among patients with RA. By treating sleep problems either pharmacologically or behaviorally, symptoms and activity limitations associated with RA may be reduced.”  

Collaborators on the study were Jacqueline Dunbar-Jacob, Ph.D., R.N., F.A.A.N., dean, School of Nursing, and Eileen Chasens, D.S.N., R.N., assistant professor, School of Nursing.

RA is an inflammatory disease affecting about 1.3 million U.S. adults, and causes pain, swelling, stiffness and loss of function in the joints. Dis­turbed sleep has been found to be a major concern among persons with RA.

The study was funded with grants from the National Institute of Health.

New Pitt Projects Will Test Brain Computer Interfaces for People with Spinal Cord Injury

PITTSBURGH, Feb. 17, 2011 – Researchers at the University of Pittsburgh have been awarded funding for two projects that will place brain-computer interfaces (BCI) in patients with spinal cord injuries to test if it is possible for them to control external devices, such as a computer cursor or a prosthetic limb, with their thoughts.

The projects build upon ongoing research conducted in epilepsy patients who had the interfaces temporarily placed on their brains and were able to move cursors and play computer games, as well as in monkeys that through interfaces guided a robotic arm to feed themselves marshmallows and turn a doorknob.

“We are now ready to begin testing BCI technology in the patients who might benefit from it the most, namely those who have lost the ability to move their upper limbs due to a spinal cord injury,” said Michael L. Boninger, M.D., director, UPMC Rehabilitation Institute, chair, Department of Physical Medicine and Rehabilitation, Pitt School of Medicine, and a senior scientist on both projects. “It’s particularly exciting for us to be able to test two types of interfaces within the brain.”

“By expanding our research from the laboratory to clinical settings, we hope to gain a better understanding of how to train and motivate patients who will benefit from BCI technology,” said Elizabeth Tyler-Kabara, M.D., Ph.D., a UPMC neurosurgeon and assistant professor of neurological surgery and bioengineering, Pitt Schools of Medicine and Engineering, and the lead surgeon on both projects.

In one project, funded by an $800,000 grant from the National Institutes of Health, a BCI based on electrocorticography (ECoG) will be placed on the motor cortex surface of a spinal cord injury patient’s brain for up to 29 days. The neural activity picked up by the BCI will be translated through a computer processor, allowing the patient to learn to control computer cursors, virtual hands, computer games and assistive devices such as a prosthetic hand or a wheelchair.

The second project, funded by the Defense Advanced Research Projects Agency (DARPA) for up to $6 million over three years, is part of a program led by the Johns Hopkins University Applied Physics Laboratory (APL), Laurel, Md. It will further develop technology tested in monkeys by Andrew Schwartz, Ph.D., professor of neurobiology, Pitt School of Medicine, and also a senior investigator on both projects.

It uses an interface that is a tiny, 10-by-10 array of electrodes that is implanted on the surface of the brain to read activity from individual neurons. Those signals will be processed and relayed to maneuver a sophisticated prosthetic arm.

“Our animal studies have shown that we can interpret the messages the brain sends to make a simple robotic arm reach for an object and turn a mechanical wrist,” Dr. Schwartz said. “The next step is to see not only if we can make these techniques work for people, but also if we can make the movements more complex.”

In the study, which is expected to begin by late 2011, participants will get two separate electrodes. In future research efforts, the technology may be enhanced with an innovative telemetry system that would allow wireless control of a prosthetic arm, as well as a sensory component.

“Our ultimate aim is to develop technologies that can give patients with physical disabilities control of assistive devices that will help restore their independence,” Dr. Boninger said.

Sister, donating part of her liver, show the depth of love

Pittsburgh, PA, February 10, 2010–Lisa Mazza broke into tears when doctors wheeled her from her ailing sister.

But it wasn’t until she entered the operating room that her unease turned to terror.

“You see all these instruments and tools, clamps and everything, all sanitized and lined up on that blue sheet,” she said. “There were so many of them. And the breathing instruments, and all the different people in there. … It was very intimidating. It was dawning on me at that moment that I was getting ready to actually do this.”

UPMC Montefiore surgeons were about to open her abdomen, slice off 50 percent to 60 percent of her liver and transplant it into her sister, Christina, who six months before learned she has hereditary amyloidosis.

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