A Spotlight on Surgical Innovation

In the latest episode of In Pursuit, surgeon, engineer, scientist and innovator, Seth Goldstein, MD, MPhil, discusses the impact of research and innovation in pediatric surgery. From using near-infrared light technology to detect intestinal ischemia in necrotizing enterocolitis, a critical disease in premature newborns, to pioneering fluorescence-guided surgery, Goldstein shares insights into the unique challenges and solutions in the field.

Guest: Seth D. Goldstein, MD, MPhil, Pediatric General and Thoracic Surgeon, Ann & Robert H. Lurie Children’s Hospital of Chicago, Assistant Professor of Surgery, Northwestern University Feinberg School of Medicine, Associate Program Director, Pediatric Surgery Fellowship, Northwestern University McGaw Medical Center

Host: Patrick C. Seed, MD, PhD, FIDSA, Attending Physician, Infectious Disease; President & Chief Research Officer, Stanley Manne Children’s Research Institute; Children’s Research Fund Chair in Basic Science; Professor of Pediatrics (Infectious Disease) and Microbiology-Immunology, Northwestern University Feinberg School of Medicine

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Show Notes

• Pediatric surgery is a high-stakes field where technology has lagged approximately 10 years behind adult treatments, according to Dr. Goldstein. He focuses on the importance of innovation in surgical practices and brings creative and adaptive solutions to a diverse pool of patients and diseases.
• Challenges associated with innovation in pediatric surgery include technical limitations, such as surgical tools designed for adult-sized patients, and the unique ethical considerations involved when creating new practices for this vulnerable population.
• Goldstein treats diseases such as necrotizing enterocolitis through his development of fluorescence-guided surgery and utilizes near infrared light and fluorescence to improve surgical precision, safety, and outcomes.
• One of the technological advancements is the use of a handheld probe which produces a light through a gentle, non-invasive touch to the abdomen, allowing Goldstein a uniquely surgical observation, to diagnose the degree of intestinal ischemia.
• He advocates for a less invasive approach to surgical challenges by leveraging human physiology and natural processes, using the body's functions to guide contrast agents and enhance surgical procedures.
• Critical evaluation of established practices for continuous improvement is an essential part of Lurie Children’s philosophy, which Goldstein says is enhanced by strong teamwork, including the graduate biomedical engineering students who contribute their diverse perspectives and innovative solutions.

Transcript

[00:00:00] Patrick Seed, MD: This is In Pursuit, research perspectives from Ann and Robert H. Lurie Children's Hospital of Chicago. I am your host, Dr. Patrick Seed, President and Chief Research Officer of Stanley Manne Children's Research Institute, one of the nation's largest freestanding pediatric research centers. Our guest today is a surgeon-engineer-scientist who will take us inside the operating room of a major children's hospital and illustrate how identifying and solving surgical problems through research and innovation can have an exponential impact on the care and outcomes of our patients. And of course, we'll learn how he got to this point in his professional journey. Dr. Seth Goldstein is a Pediatric General and Thoracic Surgeon at Ann & Robert H. Lurie Children's Hospital of Chicago. He is also an Assistant Professor of Surgery at Northwestern University's Feinberg School of Medicine and the Associate Program Director for the Pediatric Surgery Fellowship at Northwestern's McGaw Medical Center. Seth, welcome to In Pursuit Podcast. Thanks for joining us.

[00:01:06] Seth Goldstein, MD: Oh, it's a pleasure to be here. 

[00:01:07] Patrick Seed, MD: So, I introduced you as a surgeon, engineer, and scientist. Do you want to set the stage a little for our listeners by describing where you currently focus your work in both your surgical and your research roles?

[00:01:20] Seth Goldstein, MD: I'd love to. You said the word innovator in there. That always makes me proud. That doesn't necessarily tag along with surgeon, scientist, academic surgeon in all instances, it turns out. The art and science of surgery is high stakes, and so there is a tendency to play it safe and go with what you know. And this idea that trying new things comes with uncertainty, but if we don't Think of the consequences, and especially with regards to children whose technological care over the past 30, 40 years has lagged a decade behind adults, just because of this lack of innovative spirit on top of some of the obvious technical challenges of helping the kids.

[00:02:08] Patrick Seed, MD: What kind of surgery do you do? Just what are the big categories? And similarly, let's flip over and just talk about the different areas of research that you tend to, excuse the pun, operate in. 

[00:02:18] Seth Goldstein, MD: The pediatric general surgeon is arranged to fulfill most surgical needs of a children's hospital. So, rather than a tendency to specialize in a certain disease or organ system, as we often see in other contemporary surgeons, we have very broad based practice. So, for example, that ranges everywhere from congenital anomalies, children are born with extra and without necessary body parts from time to time, those used to be lethal conditions and now are correctable, we have intensive care and then neonatal intensive care units, we have childhood cancers that are devastating to all involved, Trauma, you know, the leading cause of death in American children is trauma, not any of the other rare diseases that get much more press. And so we pride ourselves in needing to be creative for that reason, because we're over such a broad range of ages, sizes, and diseases. 

[00:03:19] Patrick Seed, MD: What about research? Where do you spend most of your time? What are the big areas that you tend to focus on? 

[00:03:24] Seth Goldstein, MD: That moniker, surgeon scientist, never made as much sense to me because surgeon is the adjective, and I think my identity is more of surgeon. So I'm looking for adjectives to describe. So maybe an academic surgeon or innovative surgeon would probably suit me better. My focus has always principally been on ideas and technologies that I can either implement right away or see a future in implementation to using in our operating rooms. 

[00:03:57] Patrick Seed, MD: Tell us a little bit about what makes the pediatric surgical space more challenging or unique from other surgical specialties, you know, when we think about big people, adults.

[00:04:07] Seth Goldstein, MD: Some of them, as I alluded to when I said technical considerations, I just mean the size of the patients. That doesn't come as a surprise to some, but there are others. If you think about what I've told you about our field, it's often comprising infrequent presentations of diseases. So, research regarding adult heart disease, a good trial might enroll 10,000 subjects. You would be lucky to pick a disease in the field of pediatric surgery that you could find a couple hundred over the course of many centers and many years. So some of it's the infrequency. There are very specific to pediatric surgery considerations with regards to innovation and research. Children are a vulnerable population. It is really interesting to get a history lesson in some of the advances in society and medicine and hear of children at the receiving end. You know, Jenner's first cowpox smallpox was just injected into the next child that came his way, and so it just has a reminder of the vulnerability of children. So, you can imagine, to try something new means having a very strong sense of the fiduciary relationship you have with that child, that child's parents, who are also concerned, and maybe the most important stakeholders. And balancing that with this idea of generating new knowledge and technology for posterity.

[00:05:38] Patrick Seed, MD: Yeah, certainly the vulnerability of children adds a big layer to some of our goals to improve healthcare for kids. I imagine there's a lot of barriers or challenges in just the devices and the technology, right, because of size, developmental stage of kids. Can you give any example? It would be great for people to sort of be with you in the operating room and to have a little bit of a vantage point to conduct surgery on, you know, an infant or a toddler when you have devices that may have been designed for a 170-pound man, right?

[00:06:12] Seth Goldstein, MD: Yes. Consider that in the operating room, we desire energy devices. to prevent bleeding. So, cutting through anything with a knife will make it bleed. Whereas, if you divide any soft tissue or organ with energy, you can apply hemostasis or bleeding stoppage power even as you're coming through it. So, we desire that and we desire minimally invasive surgery for children. Must we create large scars and prolonged recoveries if we can poke in minimally invasive instruments. The rub is that, this is our most common example, the cameras, instruments, and energy devices are made for people that many times are 10 or 20 times as large. So, we will approach the manufacturers and we will say, we would like an energy device, That fits through a three millimeter laparoscopic trocar or port. That's our route of entry. And they will say, how many units might we sell? At which point we have to say, the benefit would be great to an admittedly smaller market than you're used to, but we want to consider it. And oh, by the way, not just the size. You know full well, Pat, the adage that “kids are not just small adults.” And so even as we get interested commercial vendors, industry partners, or researchers, we will throw in a twist. Oh, and we need to do it a little bit differently because children are different. And so these just add. in combination to barriers to technology innovation.

[00:07:51] Patrick Seed, MD: Yeah, I can imagine it leads to a lot of challenges and you already referred to it, a lot of creating solutions out of what you have that may not be optimal, but you have to be sort of clever and innovative on the spot. Tell me a little bit about the areas of surgical innovation that you've focused on. What are some unique pediatric problems that you found particularly daunting and have raised some passion in you to come up with your own solutions for those? 

[00:08:16] Seth Goldstein, MD: Okay, I'd like to tell you a story about near infrared light. 

[00:08:21] Patrick Seed, MD: Excellent.

[00:08:22] Seth Goldstein, MD: But I want to go way back and sort of tell you how the research that I was involved in informed my surgical practice. So it all started with a disease that pediatric surgeons take care of called necrotizing enterocolitis. This is a really terrible intestinal ischemia of premature newborns. It comes without warning and we never know how bad it is because we can't see the bowel. But as a surgeon, it's been my job to open many abdomens and look at that bowel and remove any offending culprits. And so very early in my career, I realized that my eye knows unhealthy bowel when I see it. Why can't I figure out a way to figuratively look at it in the at risk population and see when the bad things are coming? This was around the time that those doorbells were coming out, you know, the Bluetooth doorbells that everybody has linked to their phone. I thought, oh, perhaps we can implant a Bluetooth camera or, you know, something along those lines. Just thinking, again, broadly and creatively. I came to realize that I didn't need that. The skin of the infants is so thin that I could air quotes “see through” the belly if I just used the right frequency of light. So then I liken it to this idea of us getting cell phone reception in a room with all the doors and the windows closed. We're familiar with this idea. that structures can be opaque to visible light and then pass longer frequencies through, no problem. I realized that near infrared detection of the intestinal ischemia in necrotizing enterocolitis was possible. And so, this was a real benefit of coming to a place like Lurie Children's with a Northwestern partnership. Sort of a made in Chicago story. We've got multiple neonatal intensive care units associated with our hospital and medical school, and so a large enough population that even an unusual disease can be captured, and a culture that supported research and innovation to develop this. So this near infrared detection of necrotizing enterocolitis, started in an animal model, has developed. with support into a first in human trial in our neonatal intensive care units. And I'll tell you more about that. I'm giving you context to describe the way I feel about wavelengths of light outside the visible as one of my principal stocks in trade. And what was so interesting that I believe serendipitously occurred to me over the course of my clinical career with that hat on is that operative technology to detect infrared light started to become available in the operating room. Now, why is that? That has very little to do with necrotizing enterocolitis, and more to do with the fact that something called indocyanine green, which is a fluorescent contrast agent, was becoming more and more widely available. And so here I was, armed with a whole knowledge of the powers of infrared light, and I saw very early in development, the idea that surgery could be guided by fluorescence in the operating room. Now, here is a marriage of the research I'm already working on and a clinical innovation that I think is ready immediately to help the children in front of me. And so, to finally come back around to your question of some of the innovative techniques that I'm most interested in. We have a fluorescence-guided surgery program at Lurie Children's, and this is a concept that instead of just using my eyes to interpret what's on the screen, which I call white light, that's just what we all see, white light, I can make structures, either structures that I'm interested in removing or structures that I'm interested in leaving out of harm's way, I can make them glow right under my eyes using the technology that's already available to us in the operating room. This is making operations safer, faster, overall better, taking more tumor, leaving more vital structures behind. This idea of fluorescence guided surgery is something I've put a lot of thought and effort into.

[00:12:39] Patrick Seed, MD: Yeah, it sounds really fascinating. Let's start with the necrotizing enterocolitis story and then let's move into the operating suite. So, you have a baby who is probably really premature, right? Maybe this baby isn't tolerating their feeds as well, or the abdomen's a little bit of increased size. What do you do with this near infrared light technology to detect what might be dying bowel? What are you using as the device? 

[00:13:04] Seth Goldstein, MD: First, what you have to understand is that without my probe, which I'll describe, all you can do is watch and wait and fret. We don't have great therapies, except that we know that early recognition and a lot of supportive care is usually the sauce that will avoid an operation. So my technology is constructed as a handheld probe. So a wand that one person holds in the hand, and it's a light, gentle, non-invasive touch to the abdomen, just to one side of the navel or the other. And the light comes out and is reflected off underlying structures back into the probe, which runs by the same fiber optic cable to a spectrometer. A spectrometer is a light detector. And so the spectrometer essentially gives you a curve. It is the science to what your eyes might see if you could see in that wavelength. It's a uniquely surgical observation to know that the degree of intestinal ischemia and threatened loss is absolutely proportional to a certain appearance. It starts as sort of a dusky, deoxygenated hemoglobin look and then it turns into more of a purplish look. black, necrotic look as all the anaerobic cellular pathways go crazy. And so this idea that, okay, if my eye knows what the intestines will look like as they go dark, then the spectrometer can detect that. So it takes about one second, it's a non-invasive gentle light touch to the abdomen, and I get an answer regarding the state of color, and then I have to know that that state of color is a good proxy for health.

[00:14:39] Patrick Seed, MD: Yeah, it sounds amazing. I think, you know, most people are familiar with a fetal ultrasound during pregnancy and things. Why not use ultrasound? Why wouldn't that work, right? That looks through bellies into whether it's a fetus or a liver in somebody or a kidney and other things. 

[00:14:54] Seth Goldstein, MD: It's true, but there's a piece of information that the ultrasound lacks, and that is the fact that by the time you've seen a change to the shape of something, or different amounts of fluid or air in it, that's too late in the disease process. It just so happens that the way ultrasound draws that picture won't find the early signs. And so, there are some bad signs. Varieties of ultrasound like photoacoustic imaging that I've thought about because I try to take a broad approach to this. I've come to believe it's probably light based, the answer to this early diagnosis query.

[00:15:29] Patrick Seed, MD: You referred a number of times in the journey at least of the near infrared spectroscopy to coming up with ideas and needing to see those ideas through in different stages and things. Who do you think of as a mentor, a guide, who's sort of helped you on this journey at different stages to get to being a scientist and a surgeon and an engineer?

[00:15:51] Seth Goldstein, MD: Well, my training was at Johns Hopkins Hospital in Baltimore, and I have to credit a number of my mentors there with helping me develop the skill set to be both clinician and academic surgeon. As I've come to Northwestern, interestingly, you figure this doesn't get said out loud, but the newer the idea, the less likely it is that you'll find folks around you that can guide you exactly, but the Northwestern and Lurie environments have been very supportive, for instance, when In my first in human trial, I've found myself with the data that I've collected, and, okay, these are squiggles on a page. That's how they start. But, I never wanted this to be reliant on reading the matrix, so to speak, the way we look at EKGs and quibble about different deflections of the curve this way or that way. And so, uh, I decided that an artificial intelligence machine learning approach would be the best way to approach these complex data. Well, lo and behold, we have many folks in our academic orbit that are willing mentors and collaborators with regards to the machine learning. And so that's been a remarkable journey to sort of try to start speaking that language and figure out what to do with these data and how could you turn it into something that would be beneficial in real time.

[00:17:15] Patrick Seed, MD: Yeah, the ecosystem is so much, isn't it? Right? It just takes an idea to something that you can realize it in reality. You know, I've been really impressed with biomedical engineering. It's actually become more intelligent over years. And it's sort of a paradox because the reason why I think it's gotten to be more intelligent is actually because we've, we've, we've, overcome some of the hubris we've had for a long time. I think engineering went through a stage in my observation where we thought that humans could come up with better solutions than nature already had. And I think we're now getting back to getting inspiration from nature, which to me is very intuitive. There are evolved processes that have undergone thousands, millions of years, right, to get to a solution that's optimized. So, how do we take that solution and bring it to the other places where we want to improve health, right, in these, what are non natural circumstances? Are there any examples of inspiration you've got, either from nature or from other industries, that you've said, boy, if I brought that over to this problem that really plagues me, I would get a jumpstart crossing those parallel lines, right, from one idea and one area over into something that's relevant to the problems you're seeing in kids who have surgical needs?

[00:18:30] Seth Goldstein, MD: Those are such great insights and it reminds me of an adage that I came to believe as I trained in adults, which was anytime you're in the intensive care unit, you can't outsmart the human kidney. It's almost an unnatural stages of hubris. You come up with the medications that can augment some of those functions, but the best thing you can do for a healthy kidney is let it work its process. The analogy that I would draw to some of the innovative surgical work is back to fluorescence. So, when we have wanted to know where the bile duct is or where the ureters are, for example, surgeons have invested a great deal of time and energy figuring out how to insert sharp objects into different spaces, whereas that is not ideal if we can use our own body's physiology to accomplish the same task. Our own bodies sequester fluids in those spaces without a lot of effort. So really, the trick is to give, for example, contrast agents that are either cleared exclusively by the liver, well, they will end up in the extrahepatic biliary tree without any effort, cleared by the kidney, Well, they will end up in short order in the ureters without any extra effort, and using this command of human physiology to think, okay, let's downgrade the hubris, so to speak, and sort of rely on body functions to get things where they need to be, keep things out of harm's way, etc.

[00:20:00] Patrick Seed, MD: I want to finish with asking you a little bit about the role of teamwork in all of this. I think often we talk about invention and innovation and research about an I or a me and yet so much of it's because of the team. Can you talk about something you're working on and how the team has made what you're doing more likely to be something impactful and enriching for everybody involved in motivating for all the individuals to contribute?

[00:20:26] Seth Goldstein, MD: Absolutely, and that is so easy to do in our academic ecosystem. There's no question that teams make better science. I'll tell you, that's not hard for surgeons to come to terms with because teams make operations better. That is a dance of which we consider ourselves the conductor or captain in many instances, but there are no fewer than six people in any complex operation to make it go smoothly. I mean surgeons and anesthesiologists and nurses and scrub technicians and so very quickly in our line of work you realize we don't operate literally or figuratively in a vacuum. And so that same thing is true for the research and innovation as well. Sometimes the best I can do is identify a problem space and some potential attempts at solutions and then turn to the smart folks around me. Well, the smart folks in this instance are teams of graduate biomedical engineering students that come by, identify clinical needs, and then run with those in many instances making inventions. companies, et cetera. We've got ideas like that being inculcated that there is no chance I would have had the time, energy, or know how to run with on my own.

[00:21:45] Patrick Seed, MD: Yeah. Graduate students bring a lot to the team in a lot of different ways. Both fantastic ideas, a real balance of growing knowledge and expertise that often compliments yours but also a little naivete and often adds a lot actually, right? Sometimes you get the hard question of, well, why do it that way? And we all step back and scratch our head, right, and say, I actually, I don't know. Why do we do it that way?

[00:22:08] Seth Goldstein, MD: And I've come to believe that even if the queries seem obvious, if you can't defend the way something is done with logic other than it's just the way we do it, then it deserves a real critical look.

[00:22:22] Patrick Seed, MD: Yeah, we're in agreement on that. Well, listen, Seth, I want to thank you for joining me today on the podcast. 

[00:22:27] Seth Goldstein, MD: It is absolutely my pleasure to be here. Thank you for inviting me. 

[00:22:33] Patrick Seed, MD: For more information on Stanley Manne Children's Research Institute at Ann & Robert H. Lurie Children's Hospital of Chicago, visit our website, research.luriechildrens.org.