Sam Chang: Hello, everyone. My name is Sam Chang. I'm a urologist in Nashville, Tennessee in the United States. And we are delighted to have an international colleague of great esteem join us today. We have Dr. Silvia Proietti from San Raffaele Hospital in Milan, Italy. I'm trying to pronounce those correctly. But we're very fortunate to have her today and she'll actually talk about some management with looking at upper tract tumors, laser technologies and some of, I'm sure her tips and tricks. But thank you so much Silvia for joining us and we're quite excited to have you.

Silvia Proietti: Thank you very much for this prestigious invitation. Dear Professor Chang, dear colleagues, I'm very pleased and honored to be here today and to join this interesting session of UroToday. I'm going to share my slides about the UTUC treatment. And, let's see, so which is the best laser technology for the UTUC conservative treatment? If you look at the EAU Guidelines, we don't have any guidance for the best laser technology that we have to use for the ablation of the tumor in the upper urinary tract. And again, if you look at the AUA Guidelines, there is no mention about which laser should be used. And again, if we look at the consultation of UTUC Stockholm 2018, we have just a little mention about lasers but without specific suggestions. When we talk about the laser, we have to understand the laser tissue interaction.

It is very important to understand the depth of the penetration of the laser. In nowadays, we use Thulium YAG Laser, the Holmium YAG laser, the TFL laser for the treatment of the UTUC. And the longer is the wavelength, the deeper will be the expected penetration. Also, another thing that we have to consider when we talk about the laser is the continuous wave or the pulse mode. The Thulium YAG is a laser with the continuous wave and the clinical effect is a more controlled interaction with the tissue. When we talk about the pulse mode, we have a huge vapor bubble and between the pulses we have a silence. This allows for a thermal tissue relaxation which limits its carbonization. And the TFL laser is the laser with the highest water absorption among endourological laser. And this super pulse mode enables higher pulse power compared to the Thulium YAG and leading to improved cutting efficiency and reduced carbonization.

We have a lot of papers about the Holmium YAG and the UTUC conservative treatment and we know that it's safe, it's effective. And of course, we have to consider also the low grade, the high grade of the UTUC that we are treating in order to understand also the progression-free survival. And when we use the Holmium YAG laser, we use a long pulse with 1 Joules, 10 Hz and with non-contact mode to reduce trauma to tissues and bleeding. And when we have the Holmium YAG with its high peak power that generates a vapor bubble on the fiber tip, as you can see in the video, when the vapor bubble is formed, it reaches the tissue and the determines the rupture of the tissue as well to produce a deep and narrow incision. And also when we talk about the Thulium YAG laser, we have several papers, even though they are retrospective studies. But also the Thulium YAG, when we treat the UTUC is safe and effective.

And according to this study in the lab, we compared the Thulium YAG and the Holmium YAG laser and we studied the incision depth and the coagulation area in comparison between the Thulium YAG and the Holmium YAG. If we look at the pictures, the shape of the incision of the Thulium YAG are more regular, because the continuous wave output delivers the energy more precisely. In contrast, the Holmium YAG with the pulsed emission leads to explosive vaporization of the tissue, so the incision depth is deeper. And we have also microscopic fractures and tissue dissection irregularities. According to this study, we demonstrated that the incision depth was deeper with the Holmium YAG and the coagulation area was larger with the Thulium YAG. The downsize of the continuous wave operation is the high carbonization that we have while we are performing the flexible ureteroscopy which may impair the intraoperative navigation or affect cutting precision. And also, another drawback of the Thulium YAG is related to the huge amount of the necrotic tissue that we have when we use this laser on the tumor.

And sometimes, we have the laser tip stuck on this necrotic tissue. We need to enter inside the ureteral access sheath several time. And also, we cannot understand very well if there is a tumor left in this necrotic tissue. The group of professor Breda invented this new technique to combine the Holmium YAG with the Thulium YAG. They start with the Thulium YAG. They reduce the volume of the tumor. Then, they use the Holmium YAG for the removal of the necrotic tissue and they use again the Thulium YAG if they need to coagulate the tissue. Of course, you need two laser machines or a machine that combines this two technologies. And when we talk about the TFL laser, we have the first generation TFL that is a pulse classic continuous mode. It was really similar to the Thulium YAG but the second generation of the Thulium fiber laser is with a peak power higher and is all new like effect on the tissue.

If you look at this paper or the group of Professor Traxer, they compare the Holmium YAG and the Thulium fiber laser on the tissue of the pigs. And they demonstrated that the TFL is more superficial compared to the Holmium YAG but with a greater coagulation area compared to the Holmium YAG. And we demonstrated also according to our study in the peaks again that the TFL laser has an incision depth deeper than the Thulium YAG. But the Thulium YAG has a larger coagulation area compared to the TFL laser. The TFL seems to be a good compromise between the excellent hemostasis of the Thulium YAG and the tissue cutting ablation of the Holmium YAG with an acceptable degree or carbonization. If we look at these two videos that compares Holmium YAG with the TFL, when we perform the biopsy of the tumor, of course, we have some bleeding inside the kidney but it's not really important from a hemodynamical point of view.

But it's really annoying when you perform flexible ureteroscopy, you can miss some tumor when the visibility is not really perfect. When you work with the TFL laser, you work completely in a bloodless field that is really important for the treatment of this tumor in the upper urinary tract. We just sent to journal this study about the TFL laser and we enrolled 28 patients with the UTUC and we demonstrated that the TFL is safe and effective. We didn't experience any complication during one year follow up. But of course, we need prospective randomized study in a larger population with longer term of follow up with different laser sources in order to understand which is the best laser for the conservative UTUC treatment. Thank you very much for your attention.

Sam Chang: Silvia, that was incredible. I learned more in just those few minutes. As an oncologist that uses some of these laser fibers, I don't use every day the different fibers as you treat stones, as you treat soft tissues, you treat a variety of things. I learned quite a bit. My impression had always been the Thulium laser in any form YAG or the Thulium fiber laser tended to be more hemostatic was the impression that's been passed on to us. And you show those two videos side to side, in general, does it tend to be you think more hemostatic? That's pretty definitive you think?

Silvia Proietti: Yes, I perfectly agree with you. I think that the Thulium laser, Thulium YAG and TFL has better hemostasis compared to the Holmium YAG. It has been demonstrated also in the lab studies as I already showed you during this slide. But when I use the laser for the treatment of the UTUC, honestly speaking, TFL laser seems to be better compared to Thulium YAG, because the hemostasis for sure with the Thulium YAG is fantastic. But you have the problem of the necrotic tissue while you are performing flexible ureteroscopy. And believe me, when you have the tip stuck on the necrotic tissue is really annoying, because it can annoy the ablation or the tumor. You have to remove the laser fiber from the scope and enter again or you have to remove the flexible ureter scope from the ureteral access sheath. In my opinion, really, the TFL laser seems to be a good compromise between the ability of ablation of the Holmium YAG and the ability of the hemostasis and coagulation of the Thulium YAG.

Sam Chang: Yeah, I think, the video that you showed, especially when you showed the Thulium YAG sticking on the tissue and I was just thinking and you were saying how it adds time, drawing it in and out, cleaning it. But then I think your point, I think was a really important one. It obscures the visualization of what tumor, what have you treated, what have you not treated? And I think that only adds to not only risk, but also you add some more time, "Oh, did I treat? Is it treated?" You treated again and so I think those are really important points. If you know upfront, and you may not know this, are there significant cost differences, Silvia, between the fibers? You may not know the answer I because I don't.

Silvia Proietti: Honestly, I don't as well. I think TFL machine are not so expensive as high power Holmium YAG machine. Of course, we don't need high power Holmium YAG machine for the UTUC treatment because as I show you before during my presentation, you need 1 Joules, 10 Hz and long pulse duration for the Holmium YAG. For the Thulium YAG, you need 10 Watts for the treatment of the UTUC, no more I would say. But I don't know honestly about the cost of the three different laser machine.

Sam Chang: Right. And then, I would assume that the fibers are probably about the same in cost too. I don't know either. But as you look at the different fiber types and how you treat, do you think for larger bulkier tumors that perhaps that TFL is the best combination? But for small tumors, it probably doesn't make much difference, do you think that makes sense?

Silvia Proietti: It makes sense. But of course, if you have a Ferrari you want to use it every time, also, to go to the supermarket. But in the majority of centers, they have Holmium YAG laser machines. Because with the Holmium YAG, you can treat stones, you can treat prostate, you can treat bladder tumor, you can treat upper urinary tract tumor. And the TFL laser machine are newer. And so, it's difficult also to buy another laser machine if you have already one that works perfectly for so many things. It's difficult to ask another laser machine to an additional cost just because it's better for the UTUC conservative treatment. And also, we have to keep in mind that UTUC is not very common disease. And at least in Italy, we treat the UTUC in the conservative way just in referral centers, because you need the endourological armamentarium also for the treatment of this tumor. Because otherwise, you can leave some tumor inside. And of course, it's not very good for the patient that we are treating.

Sam Chang: Yeah. No. And I think that those points are essential in terms of the having all, just like you said, in armamentaria having all the possible therapies, nephroureterectomy, other treatments, evaluation, making sure that the bladders is okay. All those things I think are hugely important. I really look forward to the publication of the last set of data that you showed, because it was very, very impressive in terms of the ability to treat tumor and all the videos that you showed.

What I thought was really impressive was basically the treatment of the entire mucosa and nothing appeared to be in anything too deep or too worrisome. Really, really I think it speaks to the importance and this is what we do at our institution in Vanderbilt as well. Clearly the endoscopic surgeons, who have skills like yourself, really I think are advantageous for patients that are interested in nephron sparing, who have tumors, just as you said, for lower grade, lower risk, this really makes sense. We're more careful with higher grade. But all the points, I agree with you very, very much. Tell us where are you going to go next in your research? Are you looking at different energies, different fibers? What's next on your docket of research

Silvia Proietti: About UTUC and laser?

Sam Chang: Yes.

Silvia Proietti: Okay. We are following our UTUC patient that we are treating with the TFL laser. And I would say we have to start with another lab study. We are finalize our study, but I think we are going to understand, to use again the urothelium of the pigs and to compare the Holmium YAG, the Thulium YAG and the TFL laser on the tissue and to use different power in order to understand which is the best also settings to use in the soft tissue for the upper urinary tract tumor.

Sam Chang: Wow. I mean, Dr. Silvia Proietti, you're fantastic. We are excited to see, not only your but your institution's findings and have really moved the field forward when it comes to obviously upper tract urothelial carcinoma, but endoscopic treatment of a variety of issues obviously, up within the kidneys and the ureter. Thank you so much for spending some time with us and enlightening us and looking forward to seeing you again soon and look forward to inviting you soon to UroToday with any future studies and any future research. Thank you once again.

Silvia Proietti: Thank you very much, Sam. It was really an honor for me to join this interesting session of UroToday with you. And I really appreciate to talk about UTUC conservative treatment and laser technology. Thank you so much. Thank you.

Sam Chang: Great.