Research finalist: targeted ultrasound of the tibial nerve can affect bladder function

Daniel Casella, M.D,, wants to design a bracelet that uses ultrasound waves to stimulate the posterior tibial nerve in pediatric patients with overactive and underactive bladders. “Realistically and optimistically, we might be five years away from that,” says Dr. Casella, a pediatric urologist at Children’s National Health System who has been studying the ability of ultrasound mediated neuromodulation of the posterior tibial nerve to affect bladder function. For this work, he was named a research finalist at the Pediatric Urology Fall Congress in September.

Up to 40 percent of patients seen in a pediatric urology clinic have an element of voiding dysfunction. The majority of these patients can be managed with behavior modification and conservative measures; however there is a subset of these patients who will require more aggressive therapy. With the possibilities that this research holds, he suggests ultrasound mediated tibial nerve stimulation as potentially an ideal outpatient treatment of overactive bladder and dysfunctional elimination.

What we know

The S3 sacral nerve root contains neurons that play an important role in regulating bladder function. Stimulation of the S3 nerve root with a surgically placed neurostimulator is an effective treatment for overactive or underactive bladders in adults and more recently pediatric patients. The problem: Placement of the S3 nerve stimulator is an invasive surgical procedure that requires revision or additional procedures in up to 50 percent of pediatric patients.

Another treatment: Stimulation of the posterior tibial nerve (a peripheral extension of the S3 nerve root), with an electrical current is also an effective treatment of both overactive and underactive bladders. The problem: For a durable response, the posterior tibial nerve must be stimulated with an electrical current that produces a moderate level of discomfort for 30 minutes. These treatment sessions must then be repeated weekly for approximately 12 weeks, making it very difficult to offer this therapy to pediatric patients.

New hope for patients with bladder dysfunction

Using targeted ultrasound to stimulate nerves is an area of active research within the radiology and neuroscience community. To date, studies in humans are limited, however there have been promising results when transcranial ultrasound was used to stimulate the deep brain motor centers, potentially offering a novel treatment for movement disorders such as Parkinson’s.

Dr. Casella started this research during his pediatric fellowship at Vanderbilt with the support of a $25,000 grant from the Society of Urodynamics, Female Pelvic Medicine & Urogenital Reconstruction.

Dr. Casella says: “Using an established model of bladder overactivity in rats, we demonstrated that 2-3 minutes of ultrasound stimulation of the posterior tibial nerve can suppress bladder contractions for an average of 10 minutes.”

What’s next?

Dr. Casella plans to refine his techniques in animal models and work toward designing an ultrasound probe that can be used in humans. He is hopeful that his protocol will be ready for application in a clinical trial in the next one to two years. “Ultimately our goal is to design something that can be used at home,” Dr. Casella says. Ultrasound devices can be more compact if imaging isn’t the primary use. Ideally we would like to have the ultrasound transducer in the form of an ankle bracelet attached to a generator similar in size to a smartphone.

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Cryopreservation of testicular tissue gives cancer patients fertility hope

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One of the most common causes of premature death is cancer. But today, survival rates for many childhood cancers have surpassed 90 percent and the emphasis of care has shifted from survival to quality of life after survival. That’s according to Michael Hsieh, M.D., Ph.D., who is leading the program at Children’s National Health System and getting much support from oncology and neonatology.

“One of the important aspects of quality of life is fertility,” Dr. Hsieh says. “For those adult survivors of childhood cancer who want to have children, I think it’s imperative that we do whatever we can to help them.”

The program at Children’s National, part of a multi-institutional consortium based at the University of Pittsburgh, had one of the highest recruitment of all the satellite sites for this study, which offers cryopreservation of boys’ testicular tissue. From Dr. Hsieh’s program, tissue from 11 patients has been harvested in a year and a half.

Radiation and chemotherapy are toxic to the gonads, which have testicular and ovarian function. “The idea is that if we can freeze the testicular tissue until the technology catches up in such that we can restore fertility down the road, that’s a wonderful thing. Most of these children are in grade school and not interested in having children until at least 15-20 years.”

Getting the tissue samples

For the first time, parents of young cancer patients are having this discussion, and Hsieh says they are extremely appreciative, even if they decline to participate in the study.

Young men can provide a sperm sample, which can easily be frozen. For boys who haven’t gone through puberty or boys who are not able to give a sample because they are too sick or unwilling to do so, a biopsy can collect a tissue sample, which can then be frozen.

Storing samples at a cost

Hsieh says his work also is focused on improving funding for storage of tissues. The out-of-pocket costs to store samples are several hundred dollars a year, and it can be cost-prohibitive for some patients and families.

Hsieh has applied for financial assistance from Children’s National internal funding opportunities for the program to help even the playing field.

“I don’t think it’s fair that a child who is born into a poor family is unable to participate in fertility preservation whereas a child who happens to be born more affluent is able to,” Hsieh says.

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Transitional urology bridges care for those with pediatric-onset conditions

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A hot topic at national urology meetings is how to transition patients with pediatric-onset urologic conditions as they grow into adults. Michael Hsieh, MD, PhD, is leading the way in the U.S. by serving as a bridge for patients at the first dedicated transitional urology program in the mid-Atlantic region. The Clinic for Adolescent and Adult PedIatric OnseT UroLogy (CAPITUL) is a joint venture between Children’s National and George Washington University Hospital that started two years ago.

What’s most unique about the clinic is that Dr. Hsieh has a foot in both the pediatric world of urology and one in the adult world, with clinical privileges at both institutions. He sees the full span of pediatric urology patients, including expectant moms with fetuses that have suspected urologic anomalies to adults who may have congenital conditions that require follow-up. However, he sees more teenagers and young adults than his urology colleagues both at hospitals.

The clinic’s patients have included a 19-year-old man with multiple urethrocutaneous fistulas after failed hypospadias repairs, a 25-year-old woman with cloacal exstrophy and continent urinary diversion with a urinary tract infection and stones, and a 25-year-old man with spina bifida with incontinence urethral erosion from an indwelling catheter.

A number of significant urological conditions until recently led to premature death because of medical complications, Dr. Hsieh says. Today, 90 percent of spina bifida patients live past the age of 30. “There’s a synchronized wave of patients who are all now young adults with spina bifida, and they are facing issues of reproduction and sexuality,” Dr. Hsieh says. “These are issues that pediatric urologists generally speaking are not comfortable in managing. It makes sense: It’s been many, many years since they did that type of urology.”

The program is specifically following this transitional group on conditions that are long term and that may affect fertility, such as cancer and varicoceles.

One in five teenage boys have varicoceles, or varicose veins on the scrotum. “The relationship between having varicocele as a teenager and infertility as an adult is not clear, so we felt it important to include this diagnosis in the transitional program so we can follow these patients long term and monitor their testicular growth,” Dr. Hsieh says.

Proof that the program’s working

Dr. Hsieh tracks the messages from colleagues referring patients from one institution to the other. “Unfortunately, some patients and families—for a range of issues—fall through the cracks, so it is really important to have that direct link. If we didn’t have the program set up as it is, there would be fewer successful transitions between institutions,” he says.

Another way Dr. Hsieh knows the program is working is because of the uptick in adolescent and young adult patients in his practices at Children’s and at GW.

Dr. Hsieh says the optimal time to begin transition is at age 12, when the team makes the patient and family aware of the transition policy. From ages 14-16, it’s time to initiate the health care transition plan and begin discussing the adult model of care. By age 18, Dr. Hsieh recommends the transition to adult care, and by ages 23-26, patients are integrated into adult care.