Revolutionizing Treatment for Short Bowel Syndrome with Dr. James Dunn

In this episode, host Rachel Baker interviews Dr. James Dunn, chief of the Division of Pediatric Surgery at Stanford University. Dr. Dunn is the inventor of a device that uses distraction enterogenesis to lengthen the small intestine. Join us as we delve into Dr. Dunn's innovative work on short bowel syndrome and his inspiring journey to bring new devices from bench to bedside.

Rachel Baker: [00:00:00] Welcome to Scrubcast, where we take a closer look at the research happening at Stanford University's Department of Surgery. I'm your host, Rachel Baker. Today, we're speaking with Dr. James Dunn. Welcome to the show.

Dr. James Dunn: Thank you, Rachel.

Rachel Baker: Dr. Dunn is chief of our Division of Pediatric Surgery. Did you always know you wanted to be a pediatric surgeon?

Dr. James Dunn: I was in medical school thinking that I wanted to do something surgical, but I wasn't set on pediatric surgery. But my experience in medical school really, uh, inspired me to become a pediatric surgeon. To be able to help children, saving lifetimes, doing all the interesting things that, uh, could be possible, uh, was, uh, some of the factors that made me decide to become a pediatric surgeon.

Rachel Baker: Well, I want to spend the majority of our time today talking about your work with Short Bowel Syndrome, a condition where the small intestine is [00:01:00] too short to absorb enough nutrients. This can be congenital or the result of surgery. How did you get interested in this condition?

Dr. James Dunn: When I was in medical school, we rotate, of course, on the surgical service as part of the requirements, and I saw these patients who were purposely made short gut because they have obesity and in those days the surgery for that is to bypass the intestines so they take intestine that's very proximal and plug it into intestines very distal so that a long section of the intestine is not used So in a way they create a short gut syndrome except they left a piece of the intestine behind that's not being used and—as it turns out—even though these patients lost weight, they suffer many complications as a result of that anatomy.

So, when I was in medical school, there was a bunch of patients who were getting their [00:02:00] procedure reversed, putting the intestines back together. And what I saw was really quite remarkable. The bypass intestine had shrunken down to the size of little worms and then the rest of the intestines were big. So, it was remarkable to me that you can have that dramatic of a change to the intestine By bypassing it, and then at the same time, once you reconnected together, that little defunctionalized little piece of intestine grows back to normal.

So that, that ability really intrigued me. And then when I went into residency and saw more of these children who have short gut syndrome because of diseases and not because something that's created, then that really inspired me to come up with a solution to help them. Because I have observed that the intestines are really quite adaptable.

So, if you can somehow make the intestine grow again, then you could solve this problem.

Rachel Baker: Awesome. Well, so from what I've read, there [00:03:00] really isn't a cure and the only treatment is TPN, which is pretty awful. You, however, have come up with a new treatment option for patients with short gut syndrome. What is distraction enterogenesis?

Dr. James Dunn: Sos the intestine is a tissue just like other tissues that we have in the body and they can respond to forces. A example of that that we use in surgery all the time would be the plastic surgeons putting in a tissue expander to get more skin. Mm hmm. Get more skin by gradually stretching the skin and the skin cells respond to that force by not just being stretched out, but to actually grow in numbers.

Sos we're basically using that same concept of distraction, pulling on things and making the intestine grow. So, uh, that was the whole idea of the research that subsequently [00:04:00] follow over 20 years to try to get this to work. Other people who have thought about this problem have used the drug approach. So, besides TPN, there is now a drug that can make the intestine grow also.

It's a very expensive drug, costs over $200,000 a year. And the catch is that you have to keep on using it. The moment you stop using the drug, you go back to where you are. So, it's not a very good way of treating this problem, although it does help, but it's so expensive.

Rachel Baker: Absolutely. So, you, in order to create this, uh, distraction in the small bowel, how are you doing that?

Since it's inside, you can't stretch it, I guess, sort of like skin.

Dr. James Dunn: Correct. So the way to get to the intestine is either through endoscopy, putting a scope through the intestine to get to it, or at the moment what we do is just the traditional surgery where we go in through [00:05:00] the abdominal wall, find a piece of intestine, and then the ways that this can be done are multiple approaches, but the current approach that we're using is to use a coil spring. A coil spring, once it's compressed together, we'll want to expand.

So what we do is we put this compressed spring inside a segment of the intestine so that you'll want to expand, but you can't because we purposely constrain it by putting stitches on both sides of the spring so that it can't just freely expand, but you then will impart a force from the compressed spring as it expands to lengthen that segment of the intestine.

Rachel Baker: Fantastic. You have done so many studies on this spring, uh, published paper after paper. It wasn't enough for you that you were able to lengthen the bowel. What were you looking for in these papers?

Dr. James Dunn: So, the intestine definitely lengthens, but we have to show that it actually functions. [00:06:00] It's no good just to have a longer piece of intestine that doesn't function.

And the intestine has so many functions. Not only does it absorb nutrients, it's got to be able to move things around from one end to the other. It has to have a defense system so that bacteria and things inside the intestine doesn't get through. So, we had to do lots of studies to show that all those functions are preserved.

And then, uh, even after that, the question that, for example, we had to face before we can do clinical trials is: Does this thing cause any other problems to the organism? So, uh, we first started in the rats and then we moved to large animals and pigs. And then we had to show that it doesn't cause any problems in the long term.

So, there are just so many more studies that needed to be done besides just a demonstration in one setting.

Rachel Baker: Got it. Well, so how do you take a concept? I think we call it [00:07:00] translation. How do we translate a concept from the academic laboratory to a clinical practice?

Dr. James Dunn: It's something that is really quite the long road as I have come to learn.

So, the first experiment to show that this is feasible was done over two decades ago. Wow. And at that time, um, the advice that I have, uh, received is that you got to patent it because otherwise nobody's going to pick it up to commercialize it. So, I patented it and I thought, well, okay, it's patented. Now, the rest should just be easy.

Now, that turns out to be just the very beginning of a long journey to actually bring it to the patient's bedside. So, after a patent is received and then somebody will have to believe in this enough to invest money to form the company that's necessary to take it through all the various steps. [00:08:00] So with the help of people at Stanford.

Uh, who of course are very experienced with these types of innovations and bringing ideas from the benches to the bedside, the company form, and then raising money to do all these things is super tough in the pediatric market space because children have unique problems that are small in size, unlike cancer, heart disease.

People are just not as ready to invest. in that process. So it takes more effort to be able to raise the money to get the company started. And then, um, you have to of course, uh, make a product that, uh, is, uh, not going to cause other problems. So there are lots of testings that needed to be done. And then once we have everything together, we went to the FDA to allow us, uh, to do these studies in human.

And for our particular company, of course, that time frame overlapped with the start of COVID.

Dr. James Dunn: So we [00:09:00] ran into another challenge because at that time, it was much harder to do anything because of the various restrictions that we had. So that also set us back some. But the FDA wanted us to do even more animal studies.

20, 30 papers just isn't enough for them. Oh. Another study done. So that also delayed us a bit and cost more money to get all that done. But fortunately, after all that is said and done in 2023, we were able to get the approval from the FDA to do this in patients. And then they threw us another curveball and insisted that we do adults first, which is more difficult because patients with short bowel syndrome do exist in adults, but they're not concentrated in centers.

So, you have to then scramble to find these patients to do at the adult hospital.

Rachel Baker: Right. So, your first [00:10:00] patient was an adult in 2023 placed by Dr. Joe Forrester. Were you allowed in the OR? Because I know that there are like some like weird things about hospitals and where you're allowed to be, but Stanford and LPCH are pretty close together. So, were you allowed to be there at least?

Dr. James Dunn: Yes, I was allowed, but what you refer to as these potential conflict definitely are considerable. They don't want me to be in there and influence the results. You know, they really I want to make sure that I am apart from the conduct of the study. But nevertheless, because this device has never been put into a human, it wouldn't make sense for Dr. Forrester to be all by himself.

Rachel Baker: Right. I want the expert there.

Dr. James Dunn: Exactly. So, uh, even though Dr. Forrester was trained ahead of time on how to place it, but for the very first few patients, it was super important for me to be there. So, I was there and make sure everything was done the way. [00:11:00] We have a practice and yes, it was very exciting to be able to see the device going in the patient after so many years of effort.

Rachel Baker: Fantastic. How many patients have you done to date?

Dr. James Dunn: So, we've done three patients so far. So, part of the delay is in this curveball of finding adult patients. So, in November of 2023, we did the second patient on the adult side. And that patient also did fine. But it was hard to find these patients.

So, in 2024 there were just not enough patients who could fit into the trial design, uh, to be done on the adult side and we were quite frustrated because, uh, they wanted us to do five of these adults first before we could move it forward to the pediatric patients. But there's an interesting pathway called the Compassionate Use Pathway for Patient Studies.

Uh, and in this [00:12:00] pathway, you do these clinical trials outside of the actual trial itself. So, the device is not approved by the FDA to be used. But if you believe that if a patient who really has no alternatives, then they will allow you to use the device in this compassionate use basis. So, after not being able to find more adult patients, we apply to the FDA to be able to do a pediatric patient who we believe would benefit from this device in this compassionate use pathway.

So, in June of this year, uh, 2024, we were able to do our very first pediatric patient.

Rachel Baker: That's awesome. Congratulations.

Dr. James Dunn: Thank you.

Rachel Baker: Well, so, you know, you said you've been working on this for decades. Are you, you know, clinical trials and you're just like, I'm done. This is good. Or are you still innovating?

Dr. James Dunn: We're [00:13:00] definitely still innovating. What we have is a very good start to this device, but there are many things that can be done. And there are also interesting things that we learn along the way. This pediatric patient that I just talked about received one of these device and did well. The spring was able to lengthen the intestine by a couple of centimeters, which is good, but you will not think a couple of centimeters would mean very much in their overall schema of things when normally there are hundreds of centimeters of intestine in a patient.

But remarkably, this patient came off of the parenteral nutrition support altogether. Is able to eat! So, that device did something to the patient so that the physiology of this child is completely changed. He is now eating normally, having normal [00:14:00] bowel movements. So, there's a very mysterious process that happened in this patient serendipitously, in a good way, to make this device, I think, much more powerful than we had imagined.

So rather than just adding more intestine, I think we have really changed some physiology so that all the rest of the intestine works better for this patient. So this, of course, needs to be repeated to show that this works in other patients. But if this were true, it would completely change the paradigm of how we treat these patients.

So, lots of research to come. Some of the things that the company is doing is to make a minimally invasive device. So rather than trying to place this at the time of surgery, making a hole in the intestine to insert the device, The endoscopic device that's being developed can then be inserted just through the mouth, uh, like a scope, uh, into the intestine and deploy it [00:15:00] that way.

So those are some of the things that are, uh, up and coming.

Rachel Baker: Fantastic. Well, we are at that point in every episode where we ask our guests, The same two questions and the first one is who is a surgeon you admire and why?

Dr. James Dunn: The surgeon I admire the most is Eric Fonkalsrud. He is a pediatric surgeon, not surprisingly.

He was my mentor when I was a resident. At UCLA and the way that he interacts with his patients, the way that he carries out all the things that he does is just top notch. He has patients that he operated on when they were children and have come to him when they become adults and ask him if he would deliver their babies. Um, so that is just super heartwarming and that the things that I aspire to.

Rachel Baker: Wonderful. The second question is, what is the best advice you have received in [00:16:00] 10 words or fewer?

Dr. James Dunn: Be passionate about your work and be persistent in your pursuit.

Rachel Baker: I like that. It makes a lot of sense considering how diligent, dogged even, you have been in this pursuit of getting your device to patients.

It makes a wonderful statement. Well, it has been an absolute pleasure chatting with you, but before I go, I want to ask what is next for Dr. Dunn?

Dr. James Dunn: For me, uh, I hope that, uh, everybody in our division of pediatric surgery will be able to do something that is going to contribute to the better care of our patients. Uh, I've encouraged all the faculty to develop specialty interests and to pursue things that they're passionate about, that they really are interested in and accomplish something that's audacious. 

Rachel Baker: Well, it's an exciting time at Stanford [00:17:00] Pediatric Surgery. Thanks so much for joining us today.

Dr. James Dunn: Thank you, Rachel.

Rachel Baker: And that brings us to the end of another episode. If you like Scrubcast, we hope you'll tell your friends and subscribe wherever you get your podcasts. Scrubcast is a production of Stanford University's Department of Surgery. Today's episode was produced by Rachel Baker. The music is by Midnight Rounds and our chair is Dr. Mary Hawn.