November 1, 2014

   A Publication of the James Buchanan Brady
   Urological Institute Johns Hopkins Medical Institutions

Volume V, Winter 2000
Fighting Inflammation During Surgery May Help Men Recover Potency

Arthur Burnett: What's needed is a way to "preserve, recover, regenerate, or otherwise just regain nerve function that is critical for erection."



The nerves involved in erection are gossamer-thin, exceedingly fragile, and tiny -- so small, in fact, that for more than 70 years, surgeons performing the radical prostatectomy routinely obliterated them, because they never knew they existed.


Then came the "nerve-sparing" radical prostatectomy, developed in the early 1980s by Patrick C. Walsh, M.D. Now, impotence is no longer considered an inevitable consequence of the operation: Surgeons know that if even one of the two bundles of nerves that are responsible for erection can be preserved during the surgery, it is still possible for a man to recover potency.

The problem is, even if both nerve bundles are preserved, potency -- the ability to have and maintain an erection -- is still not a certainty; also, the recovery of potency may take months. Two men the same age, with the same degree of prostate cancer can have exactly the same operation, performed with the same skill by the same surgeon: Afterward, one or both of them may be potent. There is no guarantee, and no sure-fire means of predicting. In any part of the body, whenever there is injury, there is an immune response. In an attempt to protect themselves, the nerves fight back, with inflammationheat, redness, and swelling, sometimes on a microscopic level. But sometimes this reaction proves more damaging than the injury itself. Urologist Arthur Burnett, M.D. believes the key to preserving potency after surgery may be to protect the nerves during it -- to quell this inflammation almost as soon as it starts.

"We have excellent rates of potency here at Hopkins," he says (see radical prostatectomy story). "But it's not 100 percent, and it can take months to recover. What accounts for that discrepancy? It may be that the nerves are inadvertently injured with traction, or even that the dissection adjacent to them somehow exposes them to injury -- something causes the nerves to sustain an inflammatory setback." If this is the case, he adds, then what's needed is a way to "preserve, recover, regenerate, or otherwise just regain nerve function that is critical for erection. "

These nerves need extra protection; they need the time and necessary ingredients to heal. They also need to be shielded from their own immune response, says Burnett, a surgeon who has also spent the last decade doing research in collaboration with the Department of Neuroscience and its director, Sol Snyder, M.D. (Their remarkable discovery, nearly eight years ago, that nitric oxide -- a chemical messenger, or neurotransmitter, that causes muscles to relax and blood vessels to dilate -- plays a crucial role in erection led to the development of the drug Viagra.) For the last few years, Burnett has been working with special proteins called neuro-immunophilins, which are being studied in a host of ailments -- stroke, Huntington's disease, and even in organ transplants -- for their ability to reduce inflammation and shield nerves from injury. He has found that, in rats with nerve injury and erectile dysfunction similar to that found in men after radical prostatectomy, using neuro-immunophilin solutions to "bathe" the nerves provides " greater preservation of erectile function, despite the injury."

Burnett's collaborator in the nitric oxide work, Sol Snyder, is renowned for his canny ability to recognize exciting work in other disciplines and find novel ways of applying it to neuroscience. And now Burnett, showing the same creativity, is drawing inspiration from a form of treatment currently used for brain tumor! implantable, timed-release, biodegradable polymer wafer the size of a nickel. He envisions leaving one or more of such wafers behind after surgery, to coat the injured nerves with a steady balm of a neuro-immunophilin compound and perhaps some growth factors, designed to keep the inflammation down and even to stimulate nerve regeneration. Slowly, like the skin of an onion, layer after layer of the wafers would peel away -- each dispensing tiny amounts of nourishing medication, gradually restoring the nerves to normal function.

But this nerve-bathing solution, no matter how restorative, can't work miracles if the nerves are not properly preserved to begin with, cautions Burnett: "Experienced surgeons know the landmarks, know how to do the surgery well. I have seen so many complications from 'gimmicky' kinds of surgery, where someone who really does not know the anatomy or how to do the procedure just tries to do it. There will never be a substitute for meticulous surgery."

 

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