Jaime Landman:  So welcome to Endourology Today. We have a very wonderful episode today. This is a great collaboration between the Endourological Society and UroToday. We always try and get you early sneak peaks of some of the most interesting manuscripts out of the Journal of Endourology, and today will be absolutely no exception.

And I'm utterly delighted that we have two giants in the field of endourology. We have Manoj Monga, who I think as of April, Manoj, you became the Chair at UCSD. Welcome to the UC family. We're delighted to have you. And he is, of course, replacing Chris Kane, who's moved to the Dean's office. Manoj needs very little introduction, a global player in endourology, and in urology, thanks to his extraordinary work at the AUA. And for discussion, we have Dr. Ralph Clayman, Professor of Urology at UCI, Dean Emeritus of the School of Medicine. For three decades, he ran the Journal of Endourology with Arthur Smith, obviously founder of the Endourology Society.

And today we're going to be discussing a very interesting article that was published by Dr. Monga. The manuscript will be published in the Journal of Endourology shortly. And it's title is, "Ureteral Wall Injury with Ureteral Access sheaths", and this was a randomized prospective trial. This was done in collaboration with Olivier Traxer, as well as Dr. Loftus out of Washington University.

I'll just give a quick summary and then we'll get some comments. There were 95 patients, which were randomized either a Cook Flexor™ or Boston Scientific Navigator™, and you did use the 12/14 size. The primary outcome was the failure to deploy or success in deployment. And a secondary outcome was an important metric, which was injuries. Overall, I think you got about 87% of your access sheaths up, Manoj.

When one access sheath wouldn't go up, you put the other one up. The Navigator went up 43% of the time when the Flexor didn't. The Cook never went up when the Boston sheath failed. The Navigator was ranked as easier to deploy, but there were no differences in your ability to deploy it, and with regards to injuries. And the injuries were rated by Dr. Monga and Dr. Traxer based on videos. And these were objective in that they were blinded as to which access sheath and what the conditions were. But about 47 or 48% had low-grade injuries. Higher-grade injuries were grade 2, 3, and 4 injuries. These were on the Traxer scale. And that was 23.9% overall with no difference between the two. So Manoj, did I do a reasonable job of summarizing this?

Manoj Monga:  Yes, you did a great job. Thank you, Jamie. And first I'd like to thank you and Ralph for taking the time to meet with me today. It's a real honor and privilege.

Jaime Landman:  So what are your thoughts? Can you give us kind of what you learned by doing this? Why'd you do this study and then what would be your take home to the listener?

Manoj Monga:  Well, first let me, if I could, thank my collaborators on the study. Chris Loftus was a student at the Cleveland Clinic and is finishing up his residency at the University of Washington. And then a number of my colleagues who are very experienced urologists at the Cleveland Clinic, both in Cleveland and in Florida. So without their efforts and collaborations, this wouldn't have been possible.

Really the theme of taking a close look at the instruments we use in the operating room is something that I picked up on during my three months with you and Ralph, during my short sabbatical in between my first time in San Diego and my subsequent move to Minneapolis. And I was invigorated by that experience and have been fortunate to continue that theme throughout a large portion of my career. Access sheaths were really being revolutionized, you could say, during that time in 2001. And so we've kept a close eye on how manufacturers have continued to innovate and evolve to try to help us help patients.

Many of the studies have been in vitro studies where we looked at certain physical characteristics of sheaths. And the main one we focused on most recently, is the buckling force. How likely a sheath is to advance up the ureter as opposed to buckling in the bladder. And so perhaps one question people might ask is, well, why did you pick these two sheaths for the study? And it was because the Cook Flexor and the Navigator HD were the two that were most resilient when it came to resisting buckling in the bladder. They were, in fact, close enough that it left us pondering, well, which one should we stock? Which one should we use in our patients? And that led to the clinical trial to really compare how well they worked in practice.

Jaime Landman:  And if you said what you learned, or did you change your practice as a function of this study, was there anything that the reader or listener should take home with them?

Manoj Monga:  So maybe the second question people might ask when reading the question is why did you use 12/14? And that would be the primary thing I would change in practices. 12/14 was my go-to sheath, partly based on studies that you led along with Jameela Raymond, who was a fellow with Ralph at the same time. And through those studies, it was shown that the 12/14 sheath was able to keep the pressures in the kidney at a reasonably low level during pressurized irrigation. So I've taken that message to heart for all these years and continue to use the 12/14.

But in this study, it was apparent to me what a difference one French makes and how an 11/13 French sheath could rescue the case when a 12/14 doesn't go up. So that was probably the main thing that I shifted to. And the second was that the Navigator was successful in a large portion of cases where the Flexor was not. So we did make a transition from using the Cook Flexor to the Boston Scientific Navigator, though I still feel that both products are very good.

Jaime Landman:  So that's fascinating. I'm glad.  That didn't come across entirely in the manuscript. So it's good that the whole point here is to get the author's insights and maybe what you learned. So Dr. Clayman did do that transition and make access sheaths from something that weren't particularly well designed. In 1999 and 2000, you did your sabbatical with Applied Medical and really, it created the contemporary version of the access sheath. After reading the manuscript, what insights or vision would you have regarding access sheaths?

Ralph Clayman:  Oh, I found it very interesting. I guess, Manoj, did anybody get any Flomax or Cialis or anything to try to pharmacologically manipulate the ureter? Even though, if you will, that is still up in the air. It has not been proven, just suggested.

Manoj Monga:  Yes. That's a great question, Ralph. And that was something that has evolved since that study was conducted. There was a small portion of patients who were on Flomax to help with passage of a proximal ureter stone. But other than that, the bulk of the patients, they were not pretreated with Flomax.

Ralph Clayman:  Okay. And then the other thing, I mean, obviously, I am a big fan of the access sheath. We've done a lot of work here trying to figure out, how can we put it up safely? And we've developed a force sensor here, and we now know that if we can keep the force under about six newtons or so, we don't see any injury. If we go above six newtons, then that's when we start to see injury.

But I was interested, I mean, you had grade 2 and 3 injuries in 24% of the cases, which would be like a PULS 3 or 4. And what is sort of fascinating to me is that the Traxer grade 3, so that's a split through the urothelium out to and through the adventitia, was more common with the Navigator, despite it being a little bit smaller at 13.9%, versus the Flexor, which is a little bit bigger at 6.5%.

So it doesn't take a whole lot of pressure to split that ureter. But I know now, that when we are using our Force Sensor, we are seeing our injury rates where you actually split through the urothelium and out to fat, that is down now in our studies to about 1.4% when we were looking at some of our percutaneous work. And so we're actually looking to try and get more and more opportunity to use a Force Sensor, develop a sheath that would buckle at a certain force so that you would not injure the ureter. Even though these injuries have yet to be shown to cause ureteral strictures. But I, like you, would leave my stents for two to three weeks if I have a Traxer 3 or a PULS 4 injury.

Manoj Monga:  Well, those are excellent points, Ralph. And our study was powered to identify a 20% difference in high-grade grouping the grade 2 and 3s together. So, unfortunately, though the numbers may appear that the Navigator was higher for the grade 3s.  There is no statistically significant difference. It could be because there is no difference, or because their sample size wasn't large enough. So if we do group 2s and 3s together, there is no difference between the two sheaths.

We do have some good news though, that we reported last year, a series of 56 patients combining our experience, and Professor Traxer's, who had high-grade, grade 2, and 3 injuries.

Ralph Clayman:  Right, right.

Manoj Monga:  And the risk of developing a stricture was the same as with people who didn't have an injury. So fortunate for urologists and for patients, that the ureter has the capacity to heal. And I suspect the stent has the capacity to act as a scaffold during those critical 10 to 14 days.

So though, almost a decade now ago, we were all shocked to see the videos from Professor Traxer. And we always like to think of how many times we are cited, if Professor Traxer could say how many times that slide has been shown at a meeting and people have cringed. That's one of the most shocking images I think that we've seen in a while. But it is good news, that if we do see that sheath if it is recognized, and if we stent for 10 to 14 days, the risk of stricture is almost the same as baseline.

Ralph Clayman:  I think the only time you get into a real problem is if you are dealing with a ureteral stone and you wind up with a split, and any fragments get into the wall of the ureter, and then you've got a real problem. Those strictures that then occur with stones in the wall, are very, very difficult to deal with.

Manoj Monga:  That's right. And really the idea of measuring the force objectively is a wonderful one from your group and from [inaudible]. And I'm hopeful that such a monitoring device will be available for all of us to be able to perform the procedure more safely. As a surrogate now, I do stop if the sheath doesn't go up within 15 to 20 seconds because that was another soft endpoint that we found that the longer we tried, the more likely an injury. 

[crosstalk 00:11:20]

Ralph Clayman:  I mean, as soon as the sheath feels stuck, that's a time to downsize. It's not like the external sphincter of the urethra that with continued pressure will eventually relax. The ureter with continued pressure just splits. And then all of a sudden it becomes very easy, which is why I think in your study, you showed that if the access was not easy, that's when you had a much higher-grade injury.

It's [inaudible] all over again. If it doesn't go easy, it doesn't go at all.

Manoj Monga:  And I think it just goes to show, that when you know you're doing something wrong, don't do it. Because the endourologists were fairly good at predicting that, oh, that was hard. And that did correlate with seeing an injury when you took the sheath out. So it's a matter of being a better quarterback and calling the play differently when you see what's facing you.

Ralph Clayman:  Right. And we've gotten to a point now with our ureterals, if we are doing a renal stone ureteroscopically, and we start out with a 16. But if that doesn't go easy, then a 14. If that doesn't go easy, then we'll go down to the 12. And if that doesn't go easy, then I just put a stent up and go home. Because what we have shown is, especially with ureteroscopy for renal stones, if you are working through an 11 French sheath, our stone-free rate with that approach was absolutely abysmal, 25%, and it took a long time to do. So we found that with the 14 or 16, our stone-free rates are in the 58% to 63% range. A 16 French, if you get it up, will save you probably about 30 minutes of time. But if you're stuck and you can't get a sheath up, just put up a stent and go home and come back another day. And usually, it's easy to place a proper size sheath.

Jaime Landman:  Ralph, so our typical access sheath is a 14/16, and we get that up about 80% of the time. By the way, 80% of the time, very safely now, because now, since I was the one with that probably 1.3% injury rate, because I pushed the seven newton mark, and you don't.  But with the seven newtons, that I think we are all respecting now, we almost have no injuries, occasionally a PULS 1. Why do you think we're getting the bigger access sheath up more often? Because we haven't definitively shown that it's the Flomax and the antibiotics.

Ralph Clayman:  I mean, that's why we've got our prospective randomized study on right now, four-way randomization, looking at Flomax, Cialis, alone, or together, or nothing. And that's really the next step to try and prove it one way or the other. Because while our retrospective study suggested that the Flomax was worthwhile, we had a subsequent study when we did the sub-analysis, we could not tell the difference between Flomax and no Flomax.

So we're still in this netherworld. And you may be right, the antibiotics may be playing a role also. But the goal is to find some way to pharmacologically get the ureter to relax so that putting up a 16 French routinely would be easy. And the question is, is 16 French the limit? If a 16 French goes up at, let's say, almost no pressure at all, why don't we have available to us an 18 or 20 access sheath?

Jaime Landman:  I love that answer because you're saying, let's just get the data before we start to speculate. 

Ralph Clayman:  Oh yeah. We don't have the data.

Jaime Landman:  Manoj, wonderful article. Keep them coming. Delighted that you're joining the UC family. And with that, we'll close this episode of Endourology Today. Thank you.

Manoj Monga:  Jamie, Ralph, thanks very much.

Ralph Clayman:  Hey Manoj, great to see you. Take good care of yourself, all right?

Manoj Monga:  Thank you. You too.