Histotripsy

Podcast Transcript

Dr. Scott Steele: Butts & Guts, a Cleveland Clinic podcast, exploring your digestive and surgical health from end to end.

Hi again, everyone, and welcome to another episode of Butts & Guts. I'm your host, Dr. Scott Steele, colorectal surgeon and president of the main campus submarket here at the Cleveland Clinic in beautiful Cleveland, Ohio. And it's always a pleasure to have a repeat guest here on Butts & Guts, and I'm very happy to welcome Dr. Choon David Kwon, who is the director of minimally invasive liver surgery here at the Cleveland Clinic in our Digestive Disease Institute. David, welcome back to Butts & Guts.

Dr. Choon David Kwon: Well, thanks for having me here.

Dr. Scott Steele: So, can you give us a reminder of your background? Where'd you train, where are you from, and how did you come to the point that you're here at the Cleveland Clinic?

Dr. Choon David Kwon: Yeah, my expertise is in liver. I've been working with the liver close to over 20 years now. Any liver oncology surgery or any liver transplant, or living donor liver transplant are my expertise among them. I specialize, especially in the minimally invasive, so I do a lot of laparoscopic and robotic surgery for liver tumors.

Dr. Scott Steele: Well, we are super excited to have you here today, and thank you for all the work you're doing. So today we're going to talk a little bit about histotripsy and how the procedure works to selectively destroy cancerous liver tissue. Can you share, at a high level, what histotripsy is for our listeners?

Dr. Choon David Kwon: Histotripsy has been around from, as a basic research, for almost two decades now. So the technology has been there. It's an ultrasonic-based energy delivery, but unlike other technologies that uses maybe deliberation of heat to destroy the cancer cells, this uses the vibration of molecules to cause microbubbles at where we target. And those microbubbles are caused by this cavitron of these ultrasonic waves. They are the ones that destroy the tumor cells. What's really different with others is that it's not a heat-generated cancer cell death, but it's a frictional cancer cell death, and that's what makes it very unique apart from any other thing.

Dr. Scott Steele: So, David, how does this histotripsy distinguish between the cancer cells and the normal, in this case, liver tissue?

Dr. Choon David Kwon: Well, the histotripsy, where the microbubbles occur, the machine doesn't distinguish that it's what the surgeon or the person who does the procedure, targets the lesion, and there's a robotic arm attached to the machine that, once we plan and target where it should be zapped, then that's where the robotic arm goes around and zaps the tumor. So wherever we design to attack the lesion, that lesion is completely dead. And another thing that is very interesting about this energy is that, apart from where the microbubbles occurred and it kills the cells, right? One millimeter on the other side, all the cells are all alive. There's no cell death on the other side of the border.

Dr. Scott Steele: So, if you're looking to get a margin, it's right around the tumor itself.

Dr. Choon David Kwon: Yes. Yeah, it is a razor-sharp resection margin.

Dr. Scott Steele: So, with liver tissue, we got cut it out, radiofrequency ablation, chemotherapy, cryotherapy. So who's a candidate for histotripsy?

Dr. Choon David Kwon: Well, with histotripsy, currently got FDA approved at the end of last year. So it's a brand new technology. Any liver tumor, it can be benign or malignant, but any tumor in the liver has been approved by the FDA to be able to use, using the histotripsy technology. Some people ask me whether pancreas or kidneys can also be treated. That's currently right now under clinical trial and has not been FDA-approved yet. So any tumors only on the liver can be treated.

Dr. Scott Steele: So, is there a certain lesion that you'll look at, left side, right side, superficial, deep, anything like that, or just anywhere? It's just picking it out?

Dr. Choon David Kwon: Well, yeah, because it's an ultrasonic device and the energy is delivered through the ultrasound when it's hidden behind the ribs or when it's hidden behind the lungs, then it's difficult to get access to that. Or when it's hidden behind let’s say, a large bowel gas, then that area cannot be targeted using histotripsy. So unlike a lot of people think, it has a very wide range of applicability; actually, the area where the histotripsy can be covered is relatively limited. Now the company has come up with an upgrade, which is going to be launched in a couple of months, that allows to have the indication a little bit more wider. And I assume probably in three, four years they'll come up with another upgrade where then probably around 70, 80% of the liver will be covered by this histotripsy technology. But as of now, barely 10% of the area of the liver can be covered by histotripsy.

Dr. Scott Steele: So as a patient out there, is there any specific prep that's needed to prepare for this procedure?

Dr. Choon David Kwon: No. So the beauty about this new technology is that it doesn't make any single scar. You don't need one single needle puncture to get a procedure done. It's like lithotripsy; when you have a kidney stone, you go into a bathtub, and they deliver the ultrasonic wave to crash the renal stone. It's a very similar mechanism, but it's just that it doesn't crash to stones, but it kills the tissue.

Dr. Scott Steele: So, truth or myth? Truth or myth, histotripsy can be done through a laparoscopic or robotic approach.

Dr. Choon David Kwon: No, you don't make any incision and you just apply the machine on top of your belly and deliver the energy, and that's it. So that's the beauty of this new device. The patients, after they recover in the recovery room, some patients have asked me, "Dr. Kwon, have you done anything on me? I don't feel anything. I don't feel like anything happened to me." So that's how noninvasive it is, and that's why I think there is huge applicability in the future.

Dr. Scott Steele: So, when the tumor is getting histotripsyd, to use it as a verb, is there a situation where the effects of those waves occur when the patient is done? Kind of like a sunburn. You go out in the sun, and you see the effects of the sun after and it shrinks with time, like radiotherapy. So is this, or does it kill it all right at that time?

Dr. Choon David Kwon: It kills all at the spot. All the cells are dead. And so what it does is like liquefies the tissue, and the liquified tissue called the lysate. Your immune cells comes up, and the scavenging cells comes up and cleans it up. And during that process, you can have a very interesting effect called abscopal effect. That means that the antigen that has been absorbed by the cells are being presented to the immune system, and suddenly the patient has an overall immune system kick that works like immune therapy. So I've had a couple of cases already that I've seen this where I zap the one on the left, but the tumor on the right started to shrink after treating only the one on the left.

Dr. Scott Steele: Wow, that's interesting. So are there any complications or risks associated with this procedure?

Dr. Choon David Kwon: So, I don't have actually yet the details of the clinical trial for the FDA approval; it has not been published yet. But from some of the talks that I had with the people that did the clinical trial, it seems like if you have a bile duct drain like ERCP drain or a percutaneous transhepatic biliary drain, then the biliary system becomes a septic environment. And they've seen a case of sepsis that happens after the histotripsy. And as I said, it's like a lysate, so it's a broth that is very easy for bacteria to grow on. So I think that's why they had some septic event. So currently, because it's so early in the adaptive phase for the clinical patients, you don't take any patients in that have biliary drains in. But other than that, if the lesions can be seen by ultrasound and can be targeted by histotripsy, we can try applying the technology.

Dr. Scott Steele: So, I know that you said that some patients can barely feel like they had anything, and where yet another patient that might have this risk of sepsis. So do you have to follow these patients or admit them in the hospital for a post-recovery phase, or can it be done as an outpatient?

Dr. Choon David Kwon: Currently, because it is so early, so we wanted to understand that the patients are safe. So they stay overnight less than 24 hours. But now we are in the transition of making a day treatment, so they get treatment in the morning, they recover in the recovery room, they take a CAT scan to verify that their lesions have been properly treated, then they can head home.

Dr. Scott Steele: So, I know we talked very briefly about this, but if they're not a candidate for histotripsy or if you choose just not to do it, what other non-invasive options are available out there?

Dr. Choon David Kwon: Well, there are many liver-directed therapies currently, and you've mentioned just a couple of minutes ago ablation Y90, radioembolization, you can have chemoembolization, you can have radio radiation from external beam radiation. So those are some of the other currently used methods that we use for treating liver tumors. So that's still there. It's just that histotripsy allows us to approach in a less invasive fashion and in the hopes of, in some cases, have abscopal effect that might possibly be a huge benefit to those patients that don't have other modalities.

Dr. Scott Steele: So, are there any advancements on the horizon when it comes to histotripsy or any of these other noninvasive treatments for liver tumors?

Dr. Choon David Kwon: As for histotripsy, one of the things that we are trying to do as a clinical, we are gathering the data right now, trying to see which tumors, because I see patients with colorectal liver metastases, I see patients with hepatocellular carcinoma, I see patients with cholangiocarcinoma, I see patients with breast cancer with liver metastases, pancreatic cancer with liver metastases. I see all different cancers that metastasize to liver that we treat with histotripsy. So right now we are in the phase of understanding which cancer group or which phenotype within a cancer group would most likely have the abscopal effect, because I think that's the group that would benefit most from this treatment.

Dr. Scott Steele: Well, now it's time for a quick kidder, a chance to get to know you a little bit better. So if you had your choice, would you choose salt or sweet?

Dr. Choon David Kwon: Salt.

Dr. Scott Steele: What was your first car?

Dr. Choon David Kwon: My first car was a Daewoo; I bought it in Korea. I actually, I made a deal with my mother when I was in high school, and she said, "If you hit certain numbers in your exam, then I'm going to buy you whatever you want." And I said, "Okay, buy me a motorcycle." And she never thought I would reach there, and apparently I reached and she's like, "Oh, oh, David, can you think twice of buying a motorcycle?" And said, "Okay, then buy me a car." So that's how I ended up buying the first car.

Dr. Scott Steele: Okay. So you've traveled the world, but tell me, what would be the best trip of a place that you have not gone to yet?

Dr. Choon David Kwon: One of the places on my bucket list is Iceland and Antarctica.

Dr. Scott Steele: That's fantastic. And so finally, if you could go back in time, back in high school, what did you think you were going to be when you grew up?

Dr. Choon David Kwon: I really didn't know much. I actually wanted to be a missionary because I was in a missionary boarding school for two years and I was living in Venezuela in the Andes Mountains. And we used to go hiking with a machete, go up in the mountains, sleep there one night, and come back. And that was so much fun during my high school years that I thought life as a missionary would be great, a lot of adventures. So I initially actually wanted to become a missionary, and that brought me to maybe I should become a doctor missionary. And that's where I got interested in medicine.

Dr. Scott Steele: Oh, that's fantastic. And so, can you give us a final take-home message for our listeners?

Dr. Choon David Kwon: Histotripsy is something very new, and whenever we have something new, everybody's really, really hyped. We think, "Yeah, it's going to change the whole world." So there are parts of histotripsy that I think is going to be a game changer, but also we have to be very conscious that it's not going to solve all the things; it's not going to be the end of cancer treatment. So we just have to understand clearly what the gains are, what the risks are, and that's all the patients that come to me. I make sure they fully understand what they're getting into, but the good thing about his histo again is that it's very noninvasive in nature. So majority of the patients that give it a second thought, majority of them say, "Okay, I'll just give it a try because there's really not much to lose. If I'm lucky and I ended up having that abscopal effect, then it's a jackpot for me."

Dr. Scott Steele: Well, that's fantastic. And so, to learn more about histotripsy or to schedule an appointment for treatment here at Cleveland Clinic, please call 216.445.8389. That's 216.445.8389. You can also visit our website at clevelandclinic.org/digestive. That's clevelandclinic.org/digestive. David, so much appreciation for joining us here on Butts & Guts.

Dr. Choon David Kwon: Well, thanks so much for the invitation. I appreciated the talk.

Dr. Scott Steele: That wraps things up here at Cleveland Clinic. Until next time, thanks for listening to Butts & Guts.