February 9, 2013

UCD surgery leaves family bereft

In the antiseptic language of government documents, she was identified only as Patient No. 2, a dying woman who agreed to undergo an experimental procedure at the UC Davis Medical Center.

First of two parts

In the antiseptic language of government documents, she was identified only as Patient No. 2, a dying woman who agreed to undergo an experimental procedure at the UC Davis Medical Center.

To her family, she was Terri Lee Bradley of Placerville, a devoted single mother with a quirky sense of humor and a hardy knack for home-improvement projects.

And then she was diagnosed at age 56 with a killer brain tumor that would change the course of numerous lives – and envelop one of California's premier academic institutions in scandal.

Terri Bradley was among three brain-cancer patients who underwent unusual surgeries at UC Davis in 2010 and 2011. The controversial treatments by two university neurosurgeons have since become the focus of multiple internal investigations and a federal probe.

Bradley's family members are the first to speak publicly about the experience, describing in detail their feelings of vulnerability, dashed hopes and deep regret.

"It was the surgeons – they were so believable. We trusted everything they said and did," said Janet Bradley, 26, the second-youngest of the woman's four daughters. "They prolonged her suffering."

The neurosurgeons are Dr. J. Paul Muizelaar, 65, and his protege, Dr. Rudolph J. Schrot, 44, who encountered the Bradley family in 2010 in the midst of crisis.

Terri Bradley, like the other two patients, was suffering from glioblastoma, an aggressive brain tumor that spreads quickly and often kills in less than 15 months.

But the doctors had a theory.

They believed that manufacturing an infection in the brain might stimulate a patient's immune system to fight the cancer. Sidestepping regulatory approval, and with no animal data or trial results from which to draw, they tested this theory on the three patients, opening their skulls and intentionally infecting them with bacteria normally found in the gut.

Two of the patients, a 56-year-old Reno man and a 61-year-old Shingle Springs woman, developed sepsis and died within weeks of their surgeries.

Terri Bradley lived the longest - just over a year - before dying in a Citrus Heights nursing home in November 2011, five days after her 58th birthday.

"She was never the same again," said Regina Bradley, 28, a mother of two and Terri's second-oldest daughter. "She had no quality of life at all."

More than a year after Terri Bradley's death, the families of the patients who consented to the controversial procedures are not a united front.

The widow of Patient No. 1 has expressed gratitude to the UC Davis surgeons. Family members of Patient 3 have notified the university through an attorney that they intend to sue.

The Bradleys, meanwhile, are still trying to sort out the catastrophic series of events that began with their mother's diagnosis in May 2010 and led them down a twisting trail of medical consultations, treatments, surgeries, complications - and agonizing decisions.

"I figured this would save her. I didn't question it," said Christina Gonzalez-Bradley, 24, the youngest daughter. "Me and Regina had high hopes that she would come through this."

A killer strikes

The disease crept up on the Bradleys like a mountain lion in the brush, fleetingly visible, then retreating again.

Looking back, the daughters say that something seemed "off" about their mom in early 2010, but it was hard to pin down. A fiercely independent woman with a stubborn streak, Terri was a sturdy provider who rarely got sick.

"She did everything herself. Her motto was, 'Who needs a man? A woman can do it.' And she did," said Christina.

Terri and her husband, Scott, had moved the family to El Dorado County in 1991 from San Diego. The couple split four years later.

For the next 15 years, at least one of the Bradley daughters was living under Terri's roof at all times.

"She couldn't escape us," said Janet, laughing, describing her mom as a homebody who lived for her daughters and grandchildren and Home Depot runs.

Aside from her daughters, Terri had few girlfriends and stuck close to her two-bedroom duplex in Placerville, tinkering with computers, gardening and spoiling her seven grandchildren. She stood 5-foot-6, had curly brown hair and rarely wore makeup, except when attending her beloved Paul Revere and the Raiders concerts.

"She could do anything," said Janet. "She could tear apart a bathroom and rebuild it and make it better."

Terri worked various jobs over the years, including a stab at building her own closet-design software company. Her estranged husband died of pancreatic cancer in 2007 and, while the couple had been apart for a dozen years, the divorce was never finalized.

She spent her last five years as custodian for two Placerville preschools, a job she seemed to love, her daughters said.

By March 2010, though, the girls began to notice subtle changes.

Terri had never been to Monterey, but a much-anticipated trip with daughters Janet and Regina was greeted flatly, and a tour of the fabled Monterey Bay Aquarium seemed humdrum.

By early May, as winter yielded to spring in the Sierra foothills, the avid gardener showed little interest in helping Regina plant new bulbs. She seemed detached, disconnected, somehow dulled, doting less on her grandchildren.

The family did not know it yet, but lurking inside Terri's skull was a highly malignant brain tumor. Glioblastomas make up about 17 percent of all primary brain tumors and are more likely to strike men than women, increasing in frequency with age. Tumor cells reproduce quickly, nourished by a large network of blood vessels.

Median survival is less than 15 months.

While the tumor can present differently, experts say, Terri's early symptoms were not uncommon.

Deneen Hesser, research director for the nonprofit American Brain Tumor Association, said that many patients experience a kind of "waxing and waning" of symptoms early on while the brain attempts to accommodate its intruder. Personality changes can occur, and are sometimes accompanied by headaches, nausea, difficulty with speech and short-term memory challenges.

"The brain tumor can cause you to lose the essence of who you are – the characteristics that make you different from someone else," she said.

Eventually, though, the tumor "makes its presence well-known" - with a seizure, perhaps, or some other dramatic change, Hesser said.

For Terri, the defining moment came in May 2010, when she awakened from a nap on the floor to find that her left leg was numb. She suspected a stroke. Panicked, she called Janet, then Regina, and was rushed by ambulance to Marshall Medical Center in Placerville, less than a mile from her duplex. By then, her left arm also was numb.

Christina was alone with her mom in the emergency room when the doctor delivered the grim news. A CT scan had revealed a 3.6-centimeter mass in her right cerebral cortex.

Christina burst into tears.

"She looked right at me," said her daughter, a mother of three. "You could tell she was scared, but she was also worried about us."

All four daughters pressed into the emergency room, ignoring staff pleas to hold it back to one family member only. The Placerville physician recommended a consultation at UC Davis Medical Center, 40 miles away in Sacramento.

The family readily agreed.

From that moment forward, life changed irrevocably for the Bradley women – and particularly for Janet, who would accompany her mother to every medical appointment over the next 18 months.

"I just wanted her to not have brain cancer," Janet recalled. "I just wanted her to be my mom again. I didn't want her to die."

Doctors pursue a theory

At the time of Terri Bradley's diagnosis in May 2010, Dr. J. Paul Muizelaar was in his 14th year as chairman of UC Davis' neurological surgery department. That year, he earned $801,841, placing him 35th in the salary ranking of all UC employees systemwide.

Muizelaar had come to the school in 1997 via an unusual route. A native of the Netherlands, he was recruited out of Wayne State University in Detroit to head the department, even though he lacked a California medical license.

In the late 1990s, UC Davis' neurological surgery department was in disarray. The department's residency program was under threat of losing its accreditation, and "morale was low amongst both faculty and trainees," according to a letter from the school's former executive associate dean to the state medical board.

Muizelaar, the dean wrote, was "an acknowledged leader and international expert in head trauma." He described the neurosurgeon as a scholar, the author of "56 learned papers" and "a regular reviewer for several prestigious medical journals."

With that endorsement, the state medical board issued Muizelaar one of its first "special faculty permits," which allow a handful of foreign doctors considered academically eminent to practice medicine in California. Under the program, the foreign doctors' privileges are confined to the sponsoring California medical school or its formally affiliated hospitals.

Early on, Muizelaar established his willingness to push boundaries. In an August 1997 internal newsletter heralding his appointment, Muizelaar expressed his dissatisfaction with California's stringent law on informed consent, a patient's right to know the risks, benefits and alternatives prior to treatment.

"Hopefully, we can change it because many patients with head injury who are eligible for clinical trials are deeply comatose," he was quoted as saying in the former publication Matrix. "Treatment needs to be started right away, and the family is not always available."

Muizelaar had been intrigued for years by the notion that an accidental infection could actually fight brain cancer. While working at the Medical College of Virginia in Richmond, between 1981 and 1993, he said he "inherited" a glioblastoma patient who had lived 15 years after becoming unintentionally infected following surgery. He acquired another patient in Sacramento who lived more than 20 years after an infection.

"Most people believe, including myself, that people with glioblastomas who live much longer - it's (the result of) an immune response of their own body," he told The Bee in a July interview.

Muizelaar cites an Italian study published in 2011 of 197 patients with newly diagnosed glioblastoma who were treated between 2001 and 2008. Researchers found that the 10 patients who sustained accidental, post-operative infections appeared to have a "significant advantage," with a median survival of 30 months, compared to 16 months for the others.

He said he hired Rudolph Schrot as a UC Davis neurosurgery resident in 1999, then brought him on staff five years later, specifically with the idea of teaming up to explore the theory further.

In 2008, Muizelaar and Schrot made a run at getting official approval to test the infection theory on a child with a life-threatening glioblastoma.

The FDA rejected their request, saying the doctors must first conduct rigorous animal studies, not only to demonstrate safety, but also to "establish a reasonable proof of concept" for any future use in humans, according to a June 2008 email from an FDA official to Schrot.

A year later, the surgeons ordered the bacteria from a Virginia laboratory to begin a study on rats.

"These experiments will demonstrate a proof of principle that live bacteria can fight brain cancer," according to the written proposal. "There is a mixed body of literature over the past century which has explored the utility of using bacteria or bacterial factors in cancer therapy, but no animal studies using live bacteria in an animal model of brain tumor are available."

The rat study is continuing.

But it is clear that Muizelaar and Schrot had not abandoned their quest to test the theory on humans.

By 2010, they had identified two candidates.

The disease progresses

For anyone unlucky enough to be diagnosed with glioblastoma, the standard of treatment is fairly straightforward: Surgery to remove as much tumor as possible, followed by chemotherapy and radiation, according to medical experts.

Given the tumor's location in the body and highly aggressive nature, complete removal is not possible, even by the most skilled surgeons, said Dr. Santosh Kesari, the chief neuro-oncologist at the University of California, San Diego, School of Medicine.

Over time, the tumor may recur, emerging as an even more aggressive enemy. Sometimes the cells move, or migrate, giving rise to another tumor elsewhere in the brain.

With standard treatment, median survival is about 14.6 months, according to the American Brain Tumor Association.

While the prognosis is grim, it is "not hopeless," said Kesari, who specializes in treatment of brain tumors.

One 2009 study found that almost 10 percent of glioblastoma patients may live five years or longer, with survival rates continuing to improve, said Kesari. He had no comment on the UC Davis cases, though he said he was aware of "old literature" that described how some people with cancer did better after sustaining natural infections.

Kesari is encouraged by proposed new treatments and drugs for the deadly disease, which are being tested in government-approved clinical trials. These formal trials, which undergo a stringent approval process, are designed to test the safety and effectiveness of treatments that already have shown promise in laboratory studies.

Several of these experimental drugs or treatments may win approval by the U.S. Food and Drug Administration in the next few years, offering new hope to glioblastoma patients, the neuro-oncologist said.

Looking back, Janet says she cannot recall being told by Muizelaar or Schrot about any formal clinical trials – in Sacramento or elsewhere – or whether her mother might be a candidate.

She does remember the feelings of desperation and despair that washed over her in the fall of 2010 as her mother's condition worsened.

Muizelaar had removed the tumor in May, and she had gone through the rigors of radiation and chemotherapy, which made her horribly ill.

For a while, Terri was able to stay at home in Placerville, but she needed constant care, and Janet became her round-the-clock caregiver. Regina began managing her mother's finances.

Their mother was clearly depressed, crying often, and declining to eat even mashed-up baby food.

Meanwhile, the disease was advancing. By October 2010, her seizures were increasing, and imaging revealed even worse news: The tumor had returned, along with a suspicious new growth on the opposite side.

In the hospital's electronic records, Muizelaar noted that an MRI had shown "clearly recurrence of the tumor."

"Because this tumor had recurred so quickly despite maximum therapy we felt it was necessary to reoperate (sic) her and in view of this fast-growing tumor we would try something totally different. ," the surgeon wrote.

That "something different," it turns out, was the intentional infection with Enterobacter aerogenes, a bacteria commonly found in the gastrointestinal tract.

And Terri Bradley was their next candidate.

The proposal

On Nov. 18, 2010, Janet took her mother to meet with the doctors at their offices on Y Street, not far from the hospital. Terri was in a wheelchair, her left arm and left leg exceptionally weak.

By now, she had been referred to hospice care, but had rejected that suggestion and was living in a nursing home close to the medical center.

Initially, Janet recalled, only Schrot was present as he laid out a new proposal: the experimental wound-infection surgery, or what the doctors were calling "probiotic intracranial therapy."

At that meeting, Janet recalled, Schrot told them he was not sure the procedure would work - and that it did not have FDA approval. She said he also told them that another patient recently had agreed to the surgery, lapsed into a coma and might not survive.

Terri signaled Janet to take her outside, where mother and daughter puffed on cigarettes in the parking lot and weighed the options.

"She looked at me and said, 'Honey, what would you do?' And I said, 'I would do it,' " Janet said.

"She trusted them completely. Why wouldn't she, you know? Those are brain surgeons. How could she not trust them?"

Outside the doctors' office, her mother continued to smoke her Pall Malls, then said: "I'm afraid." But she had made her decision.

Janet wheeled her mother back inside, where Muizelaar had now joined Schrot in the office. Janet said the doctors made it clear that her mother was going to die soon, probably within three months.

"We didn't have a choice, because she was going to die regardless," she said.

"I asked Muizelaar what he would do, and he said, 'If it were me, I would demand that Schrot do the surgery on me.' "

The doctors presented mother and daughter with a consent form, which Janet found curious for its brevity and lack of any UC Davis letterhead. It was, she recalled, "short and simple," barely filling a page.

Maybe something good could come of all this, something that might help others someday, Janet thought.

"I kept thinking, 'What do we have to lose?'"


This story is based on interviews with family members, medical professionals and ethical and legal experts, along with documents, investigative reports and email correspondence released by the UC Davis Medical Center and the federal Centers for Medicare and Medicaid Services.

The Sacramento Bee also reviewed the medical records and autopsy report of the late Terri Lee Bradley, as provided by her family. The two neurosurgeons did not grant interviews for this story, but they previously have talked with The Bee or given statements.

COMING MONDAY: The long goodbye

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