Carl Maronich (Host): Welcome to Meaningful Medicine, a podcast by Novant Health, where doctors address questions they wish you would ask. I'm Carl Maronich. And today, joining me is Dr. David Sindram, a hepatobiliary and pancreas surgeon from Novant. And today, we're going to be talking about liver cancer, its implications and the advancements in treatment that really are shaping the future of care. Doctor, welcome to the podcast.

David Sindram, MD: Thank you, Carl. And I'm happy to be here. This is going to be a great opportunity to talk a little bit about a difficult topic. So, looking forward to it.

Host: Yes, absolutely. And maybe we can start, Doctor, by asking—I'll ask, how common is liver cancer?

David Sindram, MD: It starts by making a slight correction to your question, because the question asked about liver cancer and the location of a cancer is not always how we name a cancer. So, there is such a thing as liver cancer. That would be cancer that starts in the liver. And then, there are many cancers that maybe start elsewhere, like the colon or breast or pancreas, that then end up in the cancer.

So, to clarify that nuance is kind of important because not every cancer that ends up in the liver is called liver cancer. And we as cancer doctors really try to differentiate between the various cancers based on their site of origin, where it came from, rather than from where it went to.

Host: I see. So for this conversation, can we use the general term liver cancer, or is there a better way we can define that?

David Sindram, MD: There's probably a better way to define it. When we talk about it as medical doctors and cancer doctors, it's probably best to actually continue to talk about the cancer site of origin, where it came from, and just then talk about tumors that are either primarily starting in the liver or secondarily have ended up in the liver, and that's metastatic disease. So, we talk about it as primary liver cancer and metastatic disease that ended up in the liver. That's probably the more accurate way. And that's because when people get in touch with their doctors, regarding their own problems or own cancers, that's kind of how we talk about it. And it's an important distinction, because not every cancer that ends up in the liver is treated the same way.

Host: I see. So, let me ask then, how common is it for cancer to impact somebody's liver in that system?

David Sindram, MD: And that's a key question. That's actually a really good question. It's incredibly common. It's a common pathway of almost all cancers to end up in the liver at some point as well. So for instance, if you have a colon cancer and the colon cancer started somewhere in the length of your entire colon, somewhere there's a tumor, oftentimes the next place where cancer then spreads to is the liver. Literally, cancer cells flush into the blood flow out of the colon, and the first station that it comes to is the liver.

As a point of distinction at this stage, if a cancer were to start, for instance, in breast tissue, then the cancer that starts in the breast tissue makes it into the bloodstream as a way of spreading, has to travel through your entire body, but can eventually also end up in the liver.

Those two cancers have very different ways of approaching them because, one, it's the first station where the cancer might nestle as a form of spreading. And the second cancer that I gave as an example, that cancer may have traveled to various other places before it landed in the liver. And as such, the disease might be far more progressed and far more advanced, which would limit our ability to treat the cancer effectively once it ends up in the liver.

Host: I see. So for those individuals that cancer is now impacting the liver, what would some of the typical symptoms be and how is that diagnosed?

David Sindram, MD: The scary part, Carl—this is the scary part—where the liver doesn't really have any sort of pain fibers. So, it's not like you can feel it. It's not like a tumor in the liver would give you an obvious pain, an obvious ache. And it's often very late in the process of a patient's cancer journey that a cancer gets discovered in the liver because the only real way to find a lot of the cancers is by means of scans. You have to discover them as part of routine followup that most of us cancer doctors do, when we follow patients on their cancer journey.

So, the only other time maybe that people will recognize a symptom is when the bile ducts—those are important structures within the liver that carry some of the waste products that the liver produces back into the intestine. If some of those bile ducts get blocked off by a tumor, then somebody can turn jaundiced, can turn yellow. Having said that, that's often a very, very late sign, and not a good thing. So, the scary part of cancer that is found in the liver is that you don't know until it's oftentimes quite advanced.

Host: That is scary, as you said with the start of that. How has cancer that gets to this region been treated historically?

David Sindram, MD: Up until the 1980s, we had very, very little options. We treated patients with fairly rudimentary chemotherapy agents, treatments that would affect the whole body and, by extension, also the liver. That was pretty much all that we could do. Since the 1980s, surgeons have become more adventurous and technically a little bit more adept based on new technology and new abilities and, if I can say so, also some very daring individuals that stepped into that void. They started exploring whether surgery on the liver could help people live longer and better. And it's on the shoulders of those giants, those few individuals. And most surgeons know those guys by name, that we started exploring if maybe doing surgical procedures to the liver could help people live longer and better.

And in some cancers, like for instance colon cancer or primary liver cancer, cancer that started in the liver, we started recognizing based on those early daring adventures, that we could impact patients' lives very dramatically for the better and that we could make people live longer and better by exploring those kinds of options.

The problem was that liver surgery was still in its infancy and patients were required to undergo and endure very, very drastic operations, very big surgical incisions. We gave them names such as Mercedes-Benz or Chevron incisions that resembled the shape of the car symbols for Mercedes-Benz and Chevron; large star-shaped incisions to expose the abdomen properly and then very difficult procedures were then entertained and done to cut out large portions of the liver. Those were the first adventures, and that's not very long ago.

I mean, considering that I started my medical school and surgical journey in the '90s, remember those days. I remember studying these kind of operations and participating in them. And it's not since sort of the early 2000s that people started thinking, "Okay, if we can exert an effect by doing these big operations, by cutting out tumors, can we maybe do this slightly less invasively? Are there other ways to accomplish the same, but maybe not damage patients, as much as we are with these big operations?"

And that set off an 10, 15, now almost 20-year trajectory where technological advancements, very clever device development, and various interventional techniques have become currently mainstay. And we live in a fantastic time right now where we're at the end of that road, and now we're able to even treat liver tumors, remove them without incisions whatsoever.

So, it's an incredible journey, and I feel incredibly privileged to have been part of that and have been able to facilitate a lot of those new technologies over time, including laparoscopic liver surgery, microwave ablation, Yttrium-90, radioactive microscopically small microspheres that were injected into the bloodstream of the liver. And now, even new technologies that we call histotripsy, which is a technology that doesn't even use incisions whatsoever anymore, and it's just an incredibly brilliant use of converging ultrasound beams that we aim straight at a tumor to affect the tumor and effectively destroy it.

I think it's a glorious time for us liver surgeons. It's also a little scary from a professional perspective because as we've miniaturized all of our technologies, then maybe—just maybe—I put myself out of a job eventually. But as most cancer doctors will say that, we can put ourselves out of a job, that's actually a really good thing because it means that we are really helping patients live longer and better, and that our help is no longer needed.

Host: Doctor, let's talk a little bit about the histotripsy that you mentioned. I mean, that's new age treatment. So, talk a little bit more about if an individual were to need to have that, what would their journey look like?

David Sindram, MD: So, I think the reason why I try to put it in perspective of the historical journey of how we arrived at this point, is to kind of demystify it to some degree. Histotripsy is not a magical solution to liver cancer or cancer in the liver. it's the next iteration of trying to miniaturize or minimize the damage that we do while still trying to achieve the same goals, which is, as a liver surgeon, the goal is to destroy a liver tumor, to get it out of the liver.

So, it's not a technology that now suddenly treats the cancer in the rest of your body. It's a device. It's based on physics. It's based on very, very smart use of some of the basic principles of ultrasound technology, where we use very loud bat noise, high-frequency, high-pitched noise, sounds that we cannot hear. But if you were to synchronize those sound waves very precisely and let the sound from about a 128 precisely synchronized ultrasound elements aimed at the same point in sync, then you get something that's called amplitude amplification.

And as a result of that amplitude amplification, it's sort of an exaggerated waveform that then happens, sort of akin to standing in front of a bunch of converging loudspeakers at a rock concert, you can feel the air moving in your stomach. And if you were to make it louder than you can imagine, then you actually end up creating vacuum pulses in the space, where that sound is aiming. And that vacuum is then filled with gas that tries to fill those gaps. We call that the bubble cloud or cavitation. And that process of cavitation is so violent, but it happens at such a microscopic level because of the very high frequency of the sound, that this cavitation disrupts the cells entirely and busts them up basically and turns them protein juice.

So, it's a really remarkable way of using basic physics, and it's a really remarkable way of affecting cancer without causing any sort of damage to the surrounding structures, because only the cells that are in the crosshairs of that sound beam are being destroyed. Anything sturdier than a cell or tissues that don't contain cells, like the connective tissues in your body, they don't get destroyed by the sound wave.

And if I were to point out one of the most important and critical features of this new technology is that not just that it can destroy, but also that it can keep intact some of these sturdier structures so that we can treat over those structures and not hurt them.

And I mentioned earlier that the liver has bile ducts, for instance, where waste product of the liver collects and is transported to the liver. Those are extremely critical structures. And if we were to erase them or create holes in them or burn them shut, which is often what we had to do with previous technologies, you would throw the baby out with the bathwater. You would help somebody, but you hurt them in such a degree that that people don't enjoy life anymore and are made very sick by the procedure.

Histotripsy seems to have the amazing capabilities of not destroying some of those sturdier structures, and you can treat a cancer that has enveloped around a bile duct, for instance, and erase them without incisions and leave those critical structures intact to allow patients to continue to live their lives in a helpful, healthy way.

So, it's an advance in so many different ways. And the reason why a lot of liver surgeons, including myself, are extremely excited about this new option is exactly because of that. It allows us to treat cancers in places where we couldn't before, which then allows application of all of the other technologies that we had available to ourselves, including surgery, minimally invasive, robotic, all the things that we had available up to this point, to potentially be even more effective in conjunction with histotripsy.

So, it's not magic. It's physics. It's an incredible leap forward. But it is an iteration of multiple leaps that we've made forward. And as a result, we can now treat patients that we were never able to treat before.

Host: Yeah, amazing. I'll just say, Doctor, when I was in school, physics seemed like magic to me, but that's another story.

David Sindram, MD: It is kind of like magic, yeah

Host: Let me ask, Doctor, who qualifies for histotripsy? And what percentage of patients that have cancer affecting their liver would qualify for this?

David Sindram, MD: I think that's a crucial question. I think that histotripsy in and of itself is perhaps not something to qualify for, but something that would need to fit within the treatment strategy that we come up with as a team. I firmly believe in the multidisciplinary approach, the sitting together in a room with all the doctors that can do all the different things that we do for cancers and look at somebody's cancer needs along their cancer journey, and that may change over time. And we try to apply the best possible method of care depending on the situation that a patient is in.

So, I can go make it as straightforward and, saying, "Well, everybody's a candidate," but that's not exactly true. It's not like we can just aim this beam of sound on every tumor and it would help patients. It's still a very complex and comprehensive discussion that patients should have with their cancer treatment team about whether histotripsy would be something that would fit and can be part of their treatment journey—I guess, is the term that I like to use for that.

I think that important to know because I know that histotripsy has gained a lot of attention, and there's a lot of hope particularly that has emerged from patients and family members that deal with cancer, and they understand cancer is very scary and threatening. And for those patients, histotripsy seems so magical. That's why I perhaps use those terms. But we still need to make sure that it's right for them, and the pursuit of histotripsy in and of itself is not sufficient. It has to be seen in conjunction with other technologies. But it does offer opportunities where there weren't any before, and we are at an inflection point there that a lot of the treating physicians don't know exactly about histotripsy themselves. It's still fairly new. It's only been at this point about 4,000 patients that have been treated. So, I would encourage patients that wonder about histotripsy as part of their journey, to discuss that with their treating physicians and ask them to read up on it or maybe connect with people like me or others that have been on the early adopting sort of side of new technology to see if histotripsy is something that can fit in their doctor's treatment strategy for them.

Host: very good. Well, Dr. David Sindram, a lot of great information about some really amazing technology that's now available to cancer patients. We appreciate your time today.

David Sindram, MD: Thank you, Carl. I really hope that you never have to see me again. That's usually not a good thing as a liver surgeon in cancer. It's a serious topic. And, like I said, we unfortunately still don't have the magic cure for cancer as much. As I'm excited about being able to help people live longer and better with the help of these kind of technologies, I sincerely hope you and all the people you love never have to deal with this themselves.

Host: Well, the rewarding thing is if we should need you, you're here and you have this technology and these skills. So, we're grateful for that.

David Sindram, MD: Thank you, sir. I appreciate your time.

Host: For more information or to find a physician, visit novanthealth.org. For additional health and wellness information from our experts, visit healthyheadlines.org. If you enjoyed this podcast, please share it on your social channels and explore our entire podcast library for topics of interest. I'm Carl Maronich, and this has been Meaningful Medicine. Thanks for listening.