Jaime Landman: My name is Jaime Landman. I'm a professor at the University of California, Irvine, and today I have the great privilege of being with Dr. Ralph Clayman. Dr. Clayman was the prior Chair at the University of California, Irvine, the Dean Emeritus of the University of California, Irvine, and one of the greatest thought leaders in minimally-invasive urology. Today, I have the privilege of questioning him a little bit about what's gone on in Stone disease. I happen to know that you personally are working on a lot of things that I'd like to hear a little bit about. We're here at the AUA and what's new and exciting as you see it?

Ralph Clayman: I had the opportunity to actually go through all the abstracts on stones and there's a lot going on in the world of stone disease today. I've broken this down into some different categories. So I'll start out with a metabolic evaluation and preventing stones. It was interesting, there was a nice study that showed ... I think this was out of Vanderbilt and Ann Arbor, Dr. Ryan Hsi, and Dr. Hollingsworth ... Looking at older patients with stones, but similar findings to other patients. That is if you do the 24-hour urines, they're finding out that most people have more than one abnormality. 30% have at least three abnormalities. But it comes down to, the most common is low fluid, low urine output, low citrate, and then that's followed by high oxalate.

So what we're all talking about is diet, diet, and diet. I think that this is a message that needs to go out to all urologists taking care of their stone patients, is before even thinking about putting them on drugs or anything, to actually work on optimizing their diet and then do a 24-hour urine, so you know what they're doing on the optimal type of diet.

Again, fluids are still incredibly important. There's a new app that Dr. Streeper at Hershey and Dr. Ram at Stanford have been working with, called a Mini Sip-It, which basically plugs your app on your phone into a water bottle, a smart water bottle. With that, they were able to show that you're increasing the fluid intake in people or urine output, from 1300 up to about 2000. That's ideal. So these are just really important things without any medications whatsoever, in order to prevent the stone disease.

Jaime Landman: So I'm just going to focus on that for a second. So we call ourselves healthcare specialists and yet probably well over 99% of what we do in urology is reactive sick care. I guess it doesn't sound quite as charming, reactive sick care specialists. So in your experience, because you've been practicing decades here, what percent of your patients that you see coming in from outside practices have been given the privilege of the 24-hour urine collection and metabolic evaluation?

Ralph Clayman: It's a minority. Sadly, it's really a minority. I think that John Aslan and Fred Coe with Litholink have done a tremendous service. The results you get from those 24-hour urines really help inform you as to how to prevent your patients from forming more stones. There's a lot of questions now about that. What is really important in that? I think that at the end of the day, it's the supersaturation indices.

Ralph Clayman: What is the key that you want to get your patients under? It's difficult to say. We've been looking at that right now, at UCI. Traditionally I've said, well, you want to get them under four. But what came out of this is basically, you would like to get them under four. I can't guarantee you that you won't form a stone if you're under four. But I can guarantee that if your supersaturation is up around eight or nine, that you are going to have more stones and they're going to progress.

Ralph Clayman: So again, I would like to say that roughly about 80% of our patients, I think, are in remission, on directed medical therapy. I think the more attention you pay to the patient as a physician, the greater the patient's adherence to the dietary regimen or the medical regimen to which you've referred them.

Jaime Landman: So that's the astounding part of this true healthcare story is that a minority of patients we're seeing are getting the metabolic evaluation. But the impact is enormous, at least in our experience. You just said 80%.

Ralph Clayman: Roughly.

Jaime Landman: You've used the word, "Remission" which is typically used in the cancer scenario. But this is a pernicious disease. It causes an amazing amount of pain and suffering and I think the Wisconsin Quality of Life folks have done a great job of showing that it diminishes quality of life. So what else is new and exciting at AUA?

Ralph Clayman: Well, there was a nice paper out of London by Mr. K and Naida, looking at cystinurics and basically showing that D-penicillamine was equivalent to tiopronin to Thiola, as far as efficacy and adverse side effects. The key thing, the key takeaway D-penicillamine 25 times less expensive than Thiola. So here's an old, old medication that urologists need to know about and to potentially resurrect. Because I'll tell you, there are a lot of patients out there that have a hard time making ends meet and that's a huge difference in-

Jaime Landman: So is it just dogma and false that patients don't tolerate D-penicillamine? When you say adverse events, is that what you're referring to?

Ralph Clayman: Yeah.

Jaime Landman: Because that's what reason I thought we didn't use the less expensive-

Ralph Clayman: The adverse event is equivalent for both and that's going to be in the range of about adverse events or just not being able to stay on it. Anywhere from 30 to 36%.

Jaime Landman: This is a British study.

Ralph Clayman: Yeah. If you can get a drug that's 25 times less expensive and it works. The interesting thing in their study is, that people who failed on Thiola then, D-penicillamine and vice versa, seem to tolerate it. So at any rate-

Jaime Landman: It's good to know. We should start going back to the old standard and maybe save a few pennies.

Ralph Clayman: Yeah. A nice study out of a University of Washington University. Because the data have shown, "Do I give tamsulosin to somebody with ureteral stone?" The dogma would say, "Yeah. If they're between five and 10. But if it's less than five, probably not worth it." What they did is they looked at quality of life issues and showed that in the patients who were on tamsulosin, versus those not, their quality of life was far better. Also in their study, the stone passage rate was higher and their average stone size is only 4.7 millimeters. So again, something in favor of the tamsulosin. Another thing is the study, a beautiful study on shockwave lithotripsy. They kept their patients on tamsulosin for about three months. Much, much higher stone-free rates in the tamsulosin group, than in the control group and it's Dr. Khalid Sher, who worked with us in St. Louis.

Jaime Landman:  Absolutely.

Ralph Clayman:  But a nice study. Stone-free rates went from, at three months, absolute stone free rate on CT, from 15% to 43% for the patients on tamsulosin. Another nice review on tranexamic acid, before percs. It seems that this is a good thing to do for your patients. The intention to treat with regard to transfusion, only 11 patients. So this is a huge difference. Going with the tranexamic acid, prior to surgery in those patients, who are candidates, a good idea. It's worthwhile.

Jaime Landman: Now, how big was that study? Do you recall?

Ralph Clayman: This was a meta-analysis. So they took all the papers on tranexamic acid and they came away with that. It showed less blood loss, less hemoglobin drop, less blood transfusions, lower complication rate.

Jaime Landman: So lower, because the obvious theoretical concern is thromboembolic events. Not an issue.

Ralph Clayman: Not an issue here. The other thing that was very interesting, Brian Eisner's group out of Boston, on stent pain. As far as again, drugs and stone disease, basically showed that a triple cocktail, solifenacin, 10 milligrams, silodosin, eight milligrams, and tadalafil, five milligrams. So you've got an anticholinergic, an alpha blocker, and a Phosphodiesterase inhibitor, together resulted in better tolerance of stents. I think the take-home message here is, think about tadalafil or Cialis or something in those patients, along with your other medications to help with your stent-related discomfort.

Jaime Landman: I think this follow-up study was that they realized that the patients were so worried about paying the bills, because of all the drugs they paid for, that they weren't so worried about their stent pain.

Ralph Clayman: Maybe that was it or the tadalafil had other beneficial effects, that we can't address right now.

Jaime Landman: Perhaps a quality of life improvement.

Ralph Clayman: But at any rate, significant quality of life improvement at any rate. Nice study by Mantu Gupta, out in New York, showing that basically ibuprofen at 600 milligrams as needed, was equivalent to giving patients narcotics. So again, eliminating narcotics after your ureteroscopy.

Jaime Landman: Mantu's been doing some great work in that regard. I think it's something, with everything that's going on nationally, is so important. We do need to continue to focus on non-opiate solutions too.

Ralph Clayman: We're doing that with our patients already and for breakthrough, we send them home with Toradol, as a stronger end set. In percs, a couple things that were interesting. One was Tom Chi's work with ultrasound, access to the kidney. A nice study out of his place, showing tremendously beneficial effects to ultrasound-guided access, versus typical fluoro. In their cases, their residents were putting in a lot of the percs and were much more successful with the ultrasound technique than with the traditional, fluoroscopically guided technique.

Jaime Landman: When you say benefits, that's quicker OR times, less blood loss. How about stone-free rates?

Ralph Clayman: The stone-free rates were 71% in the ultrasound groups, 64% in the fluoroscopy group.

Jaime Landman: That's CT-based numbers?

Ralph Clayman: That was not clear from the abstract. That was not clear from the abstract.

Jaime Landman: Those are pretty good results by national standards.

Ralph Clayman: Yeah. So again, I think it's very worthwhile. I think ultrasound for urologists is key and we need to become better and better ultrasonographers. I personally think that in the ER, we should be doing ultrasonography in patients that are becoming obstructed and septic. We should put the perc tube in right there and then, and skip the OR and everything else. But that's maybe tomorrow.

Jaime Landman: My good friend Alaura was telling me that ultrasound is a very good idea.

Ralph Clayman: Yeah. Alaura is a nice person.

Jaime Landman: Yeah. Wonderful.

Ralph Clayman: Ureteroscopy, I continue to be incredulous that proven advances in Ureteroscopy continue to be ignored, as people come out with disposable urethroscopes. Because they all dress in ticky tacky and they all look just the same. The idea that there's no innovation in these scopes absolutely blows my mind. The dual lumen study that was done at UCI with you and Drew Brevik, absolutely clear that the dual lumen is better than the single lumen. Better clearance of stones among a randomized trial, 48% complete stone clearance with the dual lumen, versus only 26% with a single lumen. So this is a, "No, duh" type of thing and why we don't have disposable scopes that are dual lumen is beyond my ken, but there you are. Thulium and Holmium. Thulium, Dwayne Baldwin did a nice study out of Loma Linda, showing that the Thulium laser, 40% faster than the Holmium and became cost-effective after only 85 cases, whether you're comparing it to a 30 watt or a hundred-watt Holmium. Our work that we did that Pengbo Jiang did and was reported by Andy Armstrong.

Ralph Clayman: So what Dr. Jiang did is he basically implanted, not BegoStones, but calcium oxalate stones. So dogs make calcium oxalate stones. So real calcium oxide stones into the kidneys, bilaterally of 12 pigs, closed the Pyelotomy and then proceeded to do ureteroscopy in either Holmium or thulium laser lithotripsy. What they showed was that the thulium was 70% faster, resulted in smaller fragments, better stone clearance. I think the thulium is going to eventually become the standard, if you will, as time goes by. There was some interesting stuff with your ureteral access sheaths, by Chu and colleagues from Vancouver, showing that if you get a 15 French access sheath up, the pressures in the kidney, even if the sheath is below the UPJ, staying incredibly low. As we all know, the lower the pressure, the less the chance of Urosepsis. I was amazed by a study that-

Jaime Landman: Wait a second. I am delighted, that that study that you published with Jamil Rehman, which we did in the lab, 20 years ago, has now been confirmed. That's great news. Thanks, Ben. Literally showing the exact same thing.

Ralph Clayman: Well, sometimes, if you're too far ahead of the curve, people don't see you, so they reinvent the stuff you did. It's okay. But then, Brian Eisner and Ben Chu then also, did a paper on sepsis looking at a very large database, 109,000 patients. What astounded me is the sepsis after Ureteroscopy was 5.6%, death rate, 0.2%. That blows my mind and what it comes down to is a, keep the pressure slow. B, for goodness sakes, don't do Ureteroscopy in somebody who does not have a documented, sterile urine culture. Our rate at UCI, and this is blowing our own horn, sepsis, well under 1%. We looked at that. But again, we are very much adamant about getting the urine sterile before we proceed with any of these cases.

Jaime Landman: That is not a national standard. But we've adopted the claim and standard and do that. I do want to go back to one thing. We do have remarkably low pressures when we work. But that does not mean low irrigation pressure. I routinely will go up to 200 millimeters of mercury, on a standard pump. But as long as you have a good size access sheath, the intro cavitary pressure is low. I think the beauty of that is you get high flow, low pressure, great view, but low pressure. But it's about pressure and not the pressure coming in.

Ralph Clayman: That becomes even more so if you're using a dual lumen scope and the other lumen is not occupied.

Jaime Landman: Absolutely and it often is dripping on my feet.

Ralph Clayman: That's why I always have an extra pair of socks in my locker.

Jaime Landman: That's why I have your locker combo.

Ralph Clayman: I was wondering where those socks went.

Jaime Landman: Where's all the dry socks?

Ralph Clayman: At any rate, there are all these things that can be done. It just, there's so many things that can be done that'll make the world better. It's just a matter of a few people going, "You're right. Let's just do this." But the world moves slowly. Over 10 years, over a decade, for the laparonephrectomy to catch on. How long did it take for endourology to catch on? That was another decade. So these things move really slowly.

Jaime Landman: So essentially, other than blowing up the metabolic situation, the lithotrite situation, the endoscope technology situation, in a big overall criticism of why we're not moving fast enough, nothing's really happened at this AUA.

Ralph Clayman: No, there's a lot going on. There's stuff on AI and machine learning.

Jaime Landman: I think that's the stuff that's most exciting.

Ralph Clayman: Very exciting.

Jaime Landman: It worries me most, because I understand it the least, despite writing and publishing on it and speaking on it.

Ralph Clayman: Yeah. What can I tell you? It's sort of like what Jerry Andrial once accused me of, "He's written more than he's read." The ideal thing though is—with this machine learning and artificial intelligence—is the ability to train our machines, to detect the stones in the kidneys and be able to tell us what stone volume is. Kalin Morgan, at our place, has worked very hard on that and the program that they developed gave you volume much better than the EAU ellipsoid formula.

Ralph Clayman: I think eventually, we're going to stop talking about the longest linear dimension of a stone and start talking about ccs of stone that we're treating. Once we do that, we will be much better able to compare apples to apples. Because as you well know, an eight millimeter by three millimeter, by four millimeter stone is far different than an eight by eight by eight millimeter stone. I look forward to the day when my X-ray reports come back and says, "The patient has three stones. The volumes of the stones are ABC. The average units of the stones are ABC." Great. That's going to inform how I approach those stones.

Jaime Landman: Yeah. I don't want to get you away from AI. But a perfect example is that dual lumen study you just quoted, where if you look at the linear measurements, the stone, there was no difference in stone size between the single lumen and dual lumens. Yet, the volume was twice as high in the dual lumen, which obviously challenged that technology with twice as much stone to a blade.

Ralph Clayman: It still had outperformed the single.

Jaime Landman: It still had outperformed. But it's crazy that there was no statistical difference on linear measurement. But with, I think it was 70 or so patients-

Ralph Clayman: It was almost twofold.

Jaime Landman: It was double. Yeah. So volume is critical and I think if we're going to understand advances, we have to understand what we're treating.

Ralph Clayman: Yeah and then there's a lot of stuff on robots within the Monarch system. There are three abstracts in the AUA, all of them saying exactly the same thing. How all three got accepted is beyond my ken. But it's all about, we did this in cadavers. We had novices, seven novices and they could obtain access much quicker with the Monarch system than without it.

Jaime Landman: But as much as you could be critical, that is actually an enormous advance. Because as you know, that's an EM-based system. So electromagnetic waves are not ... Alaura likes those, he or she is comfortable with. What that system does ... And this is again in vitro, with cadavers and pigs or whatnot ... It does allow a novice to be able to hit a specific point very accurately, very easily. That's the linchpin of a good PCNL.

Ralph Clayman: But it's beyond belief that we're at a point in time, where you could have somebody in the United States, press a button and send a missile 2000 miles and drop it down a chimney and I'm standing over a patient and the kidney is 10 centimeters from me and I'm sweating bullets as to whether it's going to go in the right spot. Where's my urethroscope that has a sensor on the end of it? So if I touch a papilla, the needle goes straight to that scope.

Jaime Landman: Well, in fact, that's the system you're describing. It was just FDA approved last week and it will be introduced. The first place in the world will be at UCI. Hopefully later this year, the clinical trial will start.

Ralph Clayman: Makes imminent sense and then what I want to see is, the next step is for the robot to then control my urethroscope and my laser fiber. So I can sit down and in essence, play the urethroscope as though it were truly an instrument. Rather than sitting there wondering about how long am I going to be able to do this until my thumbs and thenar eminence fatigue and my shoulders absolutely play out.

Jaime Landman: Yes. That's also part of the Monarch system and that's why I'm having my 10-year-old son train me on his video games because it's the same controller.

Ralph Clayman: Excellent.

Jaime Landman: I'm getting lessons. We're getting ready for that.

Ralph Clayman: Well, I wish you a lot of luck and I think it's much better to shoot stones than people.

Jaime Landman: Fully agree. Well, thank you very much. Great summary of a lot of really fun and interesting things are going on at the AUA.

Ralph Clayman: It's exciting times. Things are moving ahead. For some people, they move too fast. For some people, they'll never move fast enough. I think I'm in the latter group.

Jaime Landman: I strongly agree. You are in the latter group. Thank you.