Pulse
A Life-Changer
When doctors first presented Tiffany Basiliere of Worthington, Minnesota, with the idea of implanting a sacral nerve stimulator in her 6-year-old daughter Rylie, she was frightened. Place a wire and power source under her skin near her spine? No way.
Yet Rylie, who had kidney reflux as well as an overactive bladder, was having problems with urinary incontinence as many as a half-dozen times a day. In addition, two attempts at deflux injection, a procedure in which a gel-like substance is injected at the base of the ureter to repair valve function, had failed as had a surgery to reimplant her ureter. Pediatric urologist Joel Hutcheson, M.D., of Twin Cities-based Pediatric Surgical Associates, explained to Tiffany that pressure from Rylie’s bladder not only was causing the incontinence but also was exacerbating the reflux problem. He thought that implanting the nerve stimulator to regulate the bladder might enable them to better control the reflux as well.
Still, the young mother hesitated. Six months later after another deflux attempt failed, Tiffany gave Hutcheson the go-ahead. And on June 22, Rylie underwent the first of a two-part procedure. Hutcheson implanted electric leads near her third sacral nerve, then brought them through the skin on her back and attached them to an external power source to see if the gentle pulses would help her control her bladder. “It was like night and day,” says Tiffany of the change in her daughter. After years of being unable to stay dry, the girl could now control her bladder thanks to an electrical pulse that she said felt like a butterfly beating its wings. Three weeks later, Hutcheson permanently implanted the leads and a power source.
Rylie, it turns out, is the 75th child to undergo the procedure at Children’s Hospitals and Clinics of Minnesota in Minneapolis. In 2002, Yuri Reinberg, M.D., a surgeon at Children’s and an associate professor at Mayo Clinic was the first in the nation to implant the device in a child. It has been used to treat incontinence in adults since 1997. After the first part of the procedure, the 9-year-old patient, who had been wearing diapers, went home wearing normal underwear for the first time in her life. “When you see something like that, it makes a believer out of you,” he says.
Since then, Reinberg has implanted the device in children as young as 5 years of age and as old as teenagers. About 85 percent experience less leaking and urgency, according to Pam Hollatz, R.N., who tracks patients’ progress. No one knows exactly why the device works. “We think it down-regulates or diminishes the nerve impulses to the bladder,” Hutcheson says. “It likely helps the pelvic floor relax.” And although adults need the device for the rest of their lives, children seem to outgrow the need for it. There’s speculation it may retrain them so that they can control their bladders on their own, in which case, it can be removed.
Reinberg says the children who are candidates for the device have been diagnosed with dysfunctional elimination syndrome, some combination of urinary incontinence, urinary tract infections, nocturnal enuresis, and constipation. He emphasizes that it is offered as a treatment of last resort—long after behavioral, biofeedback, and pharmaceutical approaches have been tried, and failed. As a result, only a small percentage of the patients Reinberg and his partners see for incontinence are appropriate candidates.
Word about the effectiveness of sacral neuromodulation in children is spreading. An article Reinberg co-authored appeared in the Journal of Urology in 2009, and his and another group presented on it at the recent meeting of the American Urological Association.
Reinberg says the device can change the life of a child with intractable incontinence in a number of ways. He describes children once thought to have ADHD who can suddenly focus when they no longer are worried about their bladders or those who were loners gaining the confidence to make friends. Hutcheson says he’s glad he could offer the option to a patient like Rylie Basiliere. “To be able to send her into first grade knowing that she’s not going to get teased, to me as her doctor, that is a truly gratifying experience.”—Carmen Peota
Doing the Two-Step
A year ago, Mayo Clinic reported that two patients with advanced prostate cancer were cancer-free after receiving an experimental two-part drug therapy. The patients, who were part of a clinical trial, received standard hormone therapy (Lupron), and then a week later an injection of the immunotherapy ipilimumab. The men’s PSA levels were monitored until they were deemed ready for prostatectomy. Surgeons were surprised to find their tumors had disappeared.
Although there were only two patients, researchers were excited about the findings. “The results we had aren’t seen very often in patients who have only been treated with hormonal therapy,” says Mayo urologist Matthew Tollefson, M.D., a co-investigator in the clinical trial, which enrolled 106 patients and is now wrapping up. A handful of others also have responded well to the novel therapy.
The approach is an outgrowth of work by Mayo urologist Eugene Kwon, M.D., who in the mid-1990s learned that T cells make a protein, CTLA-4, that functions as an off-switch. Researchers then figured out that if they blocked the protein when the immune system is in attack mode, an immune response can continue indefinitely. They later discovered that hormonal therapy caused T cells to accumulate in prostate tumors.
From those findings, the idea emerged for the two-step therapy: Start the immune response with the Lupron, which summons the T cells to the tumor site, and then extend it with ipilimumab, which blocks CTLA4. “It’s kind of like taking your foot off the brake pedal of the car,” Tollefson says, explaining that the challenge is keeping the immune system from going into overdrive. Tollefson and others are now exploring whether higher or different doses of one or both of the drugs might yield even better results. Although he’s hopeful, he emphasizes the work is very preliminary. “We clearly need to see this in more patients.”—Carmen Peota
“Vaccine” Gains FDA Approval
Earlier this year, the Food and Drug Administration approved a “vaccine” for advanced prostate cancer. The vaccine, Provenge (sipuleucel-T), is an immunotherapy made from the patient’s own cells. Patients’ white blood cells are collected through a process similar to blood donation; certain immune cells (dendritic cells) are separated out and exposed to a protein found on prostate cancer cells to activate them. The treated cells are then returned to the patient’s blood stream to train T cells to fight the cancer. Patients go through this process three times approximately every two weeks.
The vaccine was approved for men with advanced prostate cancer that no longer responds to hormone therapy and who have few other options available to them. According to FDA documents, approval was based on results of a randomized, double-blind, placebo-controlled study of 512 men with hormone-refractory prostate cancer, 341 of whom received the vaccine and 171 of whom received a placebo. The men who received the vaccine lived four months longer, on average, than those who received the placebo (25.8 months vs. 21.7 months). Safety studies involving 904 patients found the vaccine was well-tolerated. Mayo Clinic and the University of Minnesota were involved in clinical trials of the vaccine. Officials from the Centers for Medicare and Medicaid Services are considering whether to cover the treatment, which costs an estimated $93,000.