Alan Wein: Hi, I'm Alan Wein from UroToday, and I have the pleasure today of interviewing John Heesakkers, who's one of the true luminaries in functional urology in the world.

Do you find that the patients, when you talk to them, are more apt to be amenable to nerve stimulation when you talk about implanting it in the lower extremity than on the sacral roots? I mean, I would think that for a patient sometime that's a little scary, whereas the idea of having an implant on the posterior tibial nerve, especially one that's not batterized, that's controlled with a stimulator from the outside, would be a very attractive alternative to people.

John Heesakkers: Yeah. I think you're right, Alan. But I also think that patients don't think about that too much. If you have a patient with OAB complaints who perhaps heard once or twice about sacral nerve stimulation or tibial nerve stimulation, they don't reason like we do. So they don't realize that if they have to be tested that they have to be lying on their belly for about an hour under the local anesthesia, perhaps even a general anesthesia, then they have the implant and then that has to be tested. Most patients don't realize that that will happen, and that makes that they cannot make that comparison very well compared to tibial nerve stimulation. But I think the caregivers, the physicians, they will do that.

They think, okay, I have here an 85-year-old woman who is not very mobile and who perhaps can lay on her back for half an hour. But if I have to bring her to the ER twice in order to test her on her belly and when it's successful come back again and do the second stage of this implant, I think that's for many caregivers a bit too much and they think, okay, if I have something more simple then perhaps that would be more ideal. And I think finally patients will have the same idea. But I don't know really whether they can really make the comparison between sacral nerve stimulation and tibial nerve stimulation from a technical point of view concerning the implants.

Alan Wein: Yeah. I think a lot of times it's sort of more on the sales pitch, or what I call the sales pitch of the version you're talking about it. Now, the electrode that's charged from outside, the Revi system, I mean theoretically that should be permanent. In other words, do you ever have to replace that or not?

John Heesakkers: Not really. It is activated from the outside. So it is-

Alan Wein: Oh, no, I understand that.

John Heesakkers: ... radio frequency control. It means that if it can pick up the signals then it'll be okay. But sometimes the external part is not functioning very well or in development for a new phase or a new generation of these systems, and then it needs some time to tailor it. But normally it should be responsive to the stimulator that is made for it. And also if that is broken, you change it, then you can activate it again. The issue is a bit about fibrotic tissue around the implant, whether that will make it more difficult to reach the implant and do proper stimulation. That's what we don't know yet. But what we see in our series that after two years, the response is as good as after three months. So within two years, in the study with 155 patients, we see that the response and also the amplitudes are not changing. And that means that this issue about perhaps fibrotic tissue around the implant is not very essential.

Alan Wein: Is there any type of patient that has, let's say, overactive bladder, so body build or any condition that you would not be able to use this type of implant in? In other words the one that's charged from outside, like the Revi?

John Heesakkers: We are analyzing at this moment what the predictive factors are. And then we look at, of course, stimulation parameters but also at configuration of the bodies. And then it appears that if leg circumference at the ankle, when that's too high, then it's more difficult to have good response. So the ones that have a leg circumference that is higher than what we normally would have are not the best responders. That's what we know now.

Alan Wein: What about pudendal or popliteal stimulation?

John Heesakkers: I think popliteal is comparable to tibial nerve. If you can get there, it is part of the tibial nerve. So you can have proper responses there. Pudendal is theoretically more effective than tibial nerve stimulation because it has many afferents, especially the dorsal genital nerve. So meaning the afferents going up to the brain. If you can stimulate many afferent nerves or fibers, then the effect should be higher. That's more or less the same idea that if you do bilateral stimulation, left and right, then you should have a better response than if you do only unilateral stimulation. That also is a bit the same thing. That also goes for the dorsal genital nerve or pudendal nerve. So I think you can stimulate that well. It is tried. We also tried it. But it's not that easy to get the stimulator at the proper place where it can stay there.

Another interesting thing is that sacral nerve modulation finally was coming from trying to increase sphincter activity by stimulating the efferent. So going to the end organ, to the sphincter, for stress incontinence. And it appeared by Emil Tanagho's research that that was not that effective, but it worked on overactive bladder complaints. So the focus was afterwards on overactive bladder complaints. But there are attempts now to try to stimulate the pudendal nerve also to have good sphincteric effects and that it can also treat stress incontinence or mixed incontinence perhaps. So that's also very interesting. But so far, technically, that's still to come or to begin.

Alan Wein: Is there the possibility of a transcutaneous stimulator that works? In other words without an implant, just a direct transcutaneous stimulation.

John Heesakkers: Yeah. That is done quite often already. The transcutaneous stimulation, especially at tibial nerve, but it's also at dorsal genital nerve. There are attempts from Denmark at the moment that transcutaneous stimulate the nerve and then want to see what the effect is on the lower urinary tract. And that's also very appealing, of course, because it's without surgery, it can be done at the moment that you want it, you don't have to take something out when it's needed, et cetera. So it's very appealing when it works. The issue always with transcutaneous stimulation is that the skin acts as a quite high capacitor, so it needs quite some current in order to pass the skin in order to get to the nerve, and that makes that the stimulation quite often is painful. If there's a solution for that, then that would be also very effective.

Alan Wein: Got it. So is it possible to overstimulate a nerve? In other words, let's say a device like the Revi, it's pretty much patient controlled. Is it possible for a patient to stimulate the nerve too much so it loses its efficacy or not?

John Heesakkers: That goes a bit back to what you think that neuroplasticity is. The idea always is that if you hit a nerve discontinuously with stimulation, then it is reminded every time, again the nerve, that there is stimulation going on. And that works better than continuous stimulation because then there is adaptation of the neuro system to continuous stimulation. We don't see that that much, for instance with sacral nerve stimulation. If you do continuous stimulation, it is not better but also not worse than discontinuous stimulation. The idea would be that discontinuous stimulation is having more effect, but we don't see that that much in clinical practice. Although theoretically it makes sense to do it discontinuously. Now, that also means that if you do continuous stimulation, then that would also mean if that would be harmful then also sacral nerve stimulation would have harmful effects. And we don't see that that much at the moment. So I don't think that is very risky or dangerous.

Alan Wein: There are a lot of people with pacemakers these days. Is there any kind of device that you can use in a patient that has a pacemaker?

John Heesakkers: There are devices that are MRI compatible, and then you're more or less going in the same direction. So those can be used at the same time with going into the MRI. Together with pacemakers, I don't know. I think so far it is not advised by the companies to do it.

Alan Wein: Good. Well, that's been a great discussion of this, and actually a look to the future. I mean, what do you see the future of this? I mean, do you see the future as sacral neuromodulation or some sort of patient controlled, more peripheral neuromodulation? I mean, what do you think that we'll be doing in five years or 10 years with neuromodulation?

John Heesakkers: I think it depends very much on the efficacy of the devices. If something is good and easy to implant, I think that will be the one that will be most popular. It also depends a bit on how easy it is to implant a stimulator. I think especially with the increasing ages of the population that we like to have treatments that are more accessible also on older age. So if you have patients with OAB, with a lot of co-medication, a lot of comorbidities, we don't want to give them more drugs in order to make them happy because it only works partially and it interferes quite often with other medications. So other treatments are very welcome and if then you have something like a neuromodulator that is easy to implant, or transcutaneously can also be done, but that is effective without that much surgical skill and effort then I think that will be the one that is the winner finally.

Alan Wein: Good. Any concluding remarks at all for the audience?

John Heesakkers: Well, I think it is very good that there are new developments, technically, for neuromodulators that can be used in various spaces. I think it makes our work a bit more dynamic and we don't have to rely on treatments that are there for a longer time. We have different treatment modalities, and I think that's a very good way to continue also.

Alan Wein: Well, for the audience, you've now heard it from the Oracle, so I don't think there's a lot to say in addition. So, John, thank you so much. And thank you to the audience for listening.

John Heesakkers: You're welcome. Thank you.