Exciting endomicroscopic breakthroughs for children with rare or complicated gastrointestinal conditions
Pediatric gastroenterologist, Clifton Huang, M.D., shares fascinating insights into the advancing treatments and procedures, including endomicroscopy, that are bringing new hope for children with rare or complicated conditions.
Meet the speaker
Host: Hello and welcome to Cook Children's Doc Talk. Today we're very excited to talk about gastroenterology advancements including endomicroscopy with pediatric gastroenterologist, Clifton Huang. Dr. Huang earned his degree from Dr. José Matías Delgado University in El Salvador. He completed his residency at Miami Children's Hospital, now Nicklaus Children's, along with fellowships at Emory University's School of Medicine in Atlanta, and the Pentax Training Center, Guayaquil Ecuador, World Endoscopic Organization Outreach Center. Dr. Huang is board certified in pediatrics and pediatric gastroenterology and has published numerous works related to children with rare or complicated conditions, as well as advancing treatments and procedures, including endomicroscopy. Welcome, Dr. Huang.
Dr. Huang: Thank you, Jan. And that's a really kind introduction. Thank you for having me here today.
Host: We're so glad to have you. So can you start off with a little background on what drew you to gastroenterology?
Dr. Huang: So as a med student, I was always interested in knowing more of the GI system, the fact that we sustain life and growth by eating and drinking has always been a fascinating situation to me, even how we obtain nutrients needed from the first bite to digestion and assimilation. And it's so complex when you think about all the organs that play a part in this process, all the way from the esophagus, the stomach, the small bowel, liver, pancreas and colon. It is also interesting to me the pathology behind all the gastrointestinal diseases from malabsorption to inflammation. And I feel that to deal with this is a real challenge.
Host: So pediatric gastroenterology is your specialty and advanced endoscopic procedures are your subspecialty, can you talk a little about why you chose those?
Dr. Huang: Gastroenterology is a well rounded specialty. And I love that you can do so many things within GI. It's mostly an outpatient care with the ability to do procedures, we can do research, and so many other things. So as a GI doctor, I help patients that have lifelong conditions like inflammatory bowel disease, also known for Crohn's and colitis, or in a sense to become part of that child's life. And it allows for continuity of care. And also we have multidisciplinary team approaches that has the hope to care and establish a relationship with the patient and the family. Like any other chronic condition, our goal is always to keep our patients in remission while we secure their growth and an adequate lifestyle. On the other hand, gastroenterology has to use different type of procedures either to diagnose or to treat patients. And that's something that fascinates me. We have endoscopes and these are flexible lights with cameras that we use to investigate the GI system while the patient is under general anesthesia. Now my subspecialty within gastroenterology as you said, Jan, is advanced endoscopy. So this means that I can do minimally invasive diagnostic and therapeutic procedures starting from just a simple upper endoscopy and colonoscopy procedures to more complex procedures like ERCP, which stands for endoscopic retrograde cholangiopancreatography. This is basically a scope that is used to interrogate the biliary tree. So that's the bile duct system that connects the liver with the small bowel and also the pancreatic duct system, which is basically the duct system within the pancreas that is connected to the small bowel. Now all of our endoscopes have what we call working channels. So we can pass an array of instrumentation through those channels. And we do this to diagnose and treat for example, we can pass biopsy forceps, and this is to obtain biopsy tissue that we can send to a pathologist. And for example, if we have a bleeder we can pass different treatment tools like clips, argon gas to stop bleeding, or we can even use nets that we pass through the channel to retrieve foreign bodies. So these are just very few of the many things that we can do within GI.
Host: So speaking of other things, what other advanced endoscopic procedures do you perform now, and is there anything new coming up?
Dr. Huang: Yes, you know, apart from the EGDs or the esophagogastroduodenoscopies, colonoscopies, and ERCPs. As an advanced endoscopic center, we also do push and single balloon enteroscopies, meaning that we can advance the scope into the small bowel. And probably as you're aware, Jan, the small bowel is about 20 feet long. So this can end up being a very lengthy procedure, and especially if we also need to do intubation, like pulling out a foreign body or even obtain biopsies. We will also have endoscopic ultrasound equipment soon. And this is a special endoscope that uses high frequency sound waves to produce detailed images of the lining and walls of your digestive tract and chest, or even nearby organs such as pancreas and liver, and even lymph nodes. And probably as you're aware, as technology has advanced, think about how cell phones and their cameras are even more advanced with every year that passes with the amount of megapixels. So in a similar way, our endoscopes have advanced technology, and we have now 4k imaging, magnification, narrowband images. And one new technology that we're using in pediatrics is confocal laser endomicroscopy or CLE, which what it means is a probe that consists of fiber optic fundal, with an integrated distal lens connected to a laser scanning unit. Now this probe is passed through the working channel of any endoscope while we are doing the procedure. And we give our patients a contrast agent. In this case, we will use fluorescein. And we do this via an intravenous approach. And this will help enhance the tissue we want to question. And then we position our CLE probe in the tissue we're evaluating, and a laser is shined into the mucosa. Now the light bounces it back into the objective lens, back into the detector in the confocal system, which can process the image and will magnify it 1,000 to 1,500 times. So this is like having a live microscope in your hands while you're doing the procedure. Now this can be used in any organ like the esophagus to the small bowel or even it can be passed to the kaleidoscope that is passed through the ERCP scope to see the biliary system. So basically, we're looking into the bile duct system. Now we have the microscopic view of the tissue. But we also can see in live microscopy, the mucosa of many organs, the GI system, like villi colony creeps, even vasculature, etc.
Host: So most of our audience will be familiar with endomicroscopy in adults, but it's fairly new and children, correct?
Dr. Huang: Yes, it is. But you know, in general, most published research using CLE comes from European hospitals and centers. And this research is dated back from maybe 2005 to 2007. Now, to my knowledge in the US, we are one of two institutions doing these in children and probably the first children's hospital who is actively engaged in exploring and maximizing this technology in the GI system. Now we have an endowed chair award to research and develop this technology in pediatric intestinal endoscopy at this moment.
Host: So what are the potential applications for this technology? How are we using CLE at Cook Children's?
Dr. Huang: So potentially, we can use it to evaluate for esophagitis, Barrett's esophagus, which is rare in children, but we can check for gastritis, celiac disease. Now it needs to be explored and researched more. I have been using CLE to evaluate patients with inflammatory bowel disease, both Crohn's disease and ulcerative colitis in the small bowel and colon. And what these are, are inflammatory conditions of the gastrointestinal system. So we have been using this technology to evaluate for initial diagnosis, disease, exacerbation, or even remission. And our preliminary data shows a 95 to 97% sensitivity in diagnosing microscopic inflammation within these entities, which correlates well to conventional biopsies. So we hope soon to come with diagnostic criteria. In other words, to describe CLE findings that correlate well to histologic findings. With these, we will be able to confirm diagnosis at the endoscopy suite.
Now, CLE enables us to improve targeting the tissue to obtain conventional biopsies without missing an area that microscopically may look normal. This also means that we can obtain less biopsies and reduce costs. Now most of the time as GI doctors, we obtain biopsies, and we get a pathology report as fast as 48 hours. So it doesn't make a big difference to wait two days for the result. And many times the patient can wait. I believe that the game changer is when you can use this technology to predict treatment while you have already diagnosed the condition like, for example, if we have made a diagnosis of Crohn's disease or ulcerative colitis. But what if we can predict a response to treatment right there in the endoscopy suite? So this is a potential game changer with molecular imaging, which is using exogenous molecular probes that would specifically enhance signal tissues, not only for detection of lesions, but also for drug delivery and our drug response. So this way, we don't lose time treating with medications where patients could eventually fail treatment.
Another example of what we're doing in the sense of intervention is with food allergies. We have certain patients who present with an irritable bowel syndrome picture so they will have maybe some symptoms of abdominal pain changes in their bowel movement patterns. And they will refer to have a specific type of symptom when they eat certain foods, but their food allergy panel is negative already. So what can we offer to these patients? Well, we will do a esophagogastroduodenoscopy - or an upper endoscopy - and through the working channel, we will apply allergens. Maybe we could do up to three or four allergens, and we will, one at a time, expose these allergens in the mucosa of the patient. And then after some small amount of time, we will use our CLE to magnify the tissue, and we will see if there is an immediate live reaction. So in this way, we can prove that there might be an allergy that is not the conventional or the typical type of allergy. Now, we have done this so far in at least 10 patients, and we have seen that four out of 10 will have a positive test result. Now, this is a dramatic result because we can design a diet for them, and then the child would remain symptom free when we remove the offending allergen. So, this is what we call an atypical or non-IgE-mediated food allergy.
Host: As with any procedure, there can be adverse risks. So, overall, how safe is the procedure.
Dr. Huang: There's events within confocal laser endomicroscopy, are mostly related to the allergic properties of the contrast agents, even though they're super rare. Most reported adverse events for intravenous fluorescein are really mild, and very rarely we will see anaphylaxis - so that's a really bad allergic reaction, seizures or even shock. But within the probe itself that is used to the working channel of the endoscope, there is no risk on top of the standard endoscopy risk. So CLE overall is very safe.
Host: So what training does it required to do CLE.
Dr. Huang: I learned confocal laser endomicroscopy while I was learning advanced endoscopic procedure. And the procedure is not difficult compared to like an ERCP, which is technically challenging. But it is difficult to try to learn to interpret the images that are coming from the confocal laser processing unit. It takes time to become proficient to read these images, maybe a couple of weeks to couple months. And with time, we are able to understand how endomicroscopically, the mucosa looks comparing the normal setting to the inflammatory or pathologic setting. I think that I have a good understanding right now regarding the small bowel, the colon, and the stomach, I still feel that I'm learning to assess the mucosa from the esophagus and the biliary duct system. Now, we all have to take an online course and take a small test after and then we have to be proctored for a few cases. I'm hoping that in the near future we can have our entire GI physicians being able to do endomicroscopy.
Host: So all of this sounds like such an amazing breakthrough. Yet, you are one of the few, or maybe the only, pediatric GI doctor in the nation doing this. Can you share some of the barriers to broadening its use and what's being done to change it?
Dr. Huang: As every new technology, Jan, we have two main challenges. On the one hand, there is not enough research and data, and especially in childrenm so definitely we have to create diagnostic criteria that is proved by research. And it has to be compared to the standard which is normal, histologic, or conventional biopsies. Now, just to give you an example, how does the normal esophagus looks under CLE versus using eosinophilic esophagitis. And this is just much more than we need to learn. At Cook Children's this is what we are trying to work on. Once we have set diagnostic findings for what is considered normal versus abnormal, we will proceed with molecular imaging techniques. Again, it will take some time. Our second challenge is the matter of insurance companies approving this procedure. Most commercial insurance may only approve CLE for the upper endoscopy portion, and not the colonoscopy versus others will not approve it at all. So to get the case approved, it requires a lot of discussions with the insurance directors and doing a lot of peer-to-peer evaluation. So I believe that that will get better with time.
Host: This is such a fascinating conversation, and I wish we had more time. But one more question before we close. If you could predict the future of pediatric gastroenterology, what would it look like?
Dr. Huang: That's a really broad question. And I will probably need more than few minutes to answer that. But I will just give you my personal thoughts. The future of pediatric gastroenterology and medicine in general will be to deliver individualized care that is tailored to the needs of the patient. So how are we going to be doing this? Well, we'll have to first gather as much information during the patient initial encounter. And as it becomes more available, we'll be able to evaluate the patient's genome and microbiome and obtain very individualized information from the patient's condition. The pediatric gastroenterologist may need to obtain diagnosis with state-of-the-art endoscopic procedures. So, no doubt that the technology we have in our endoscope is significantly advancing. So consider in the future we might have endoscopes could offer a 360 degree, high-definition view with magnification and embedded artificial intelligence. This sounds fascinating. Again, this will help us to obtain precise diagnosis and decrease the risk of missing pathology. The end of microscopy will open the way to molecular imaging. Now molecular imaging, think about in vivo drug trials and response. This will give us an entrance into individualized therapy to the specific phenotype of the patient that we're caring for. Also in the future, we might need to use nano medicine which can test different drugs in individualized organs for potential therapy. And then we will do point-care testing which will offer to treat the patient with an adequate dose. As this patient is followed, he or she will need to be cared by a multidisciplinary care team. So think about multiple health care professionals who can offer their expertise to care for the individual human being. Now in the future, I also believe that the pediatric gastroenterologist will need to focus on real-time problems in our community. This includes obesity and fatty liver diseases, among some. As a society, we will need to collaborate with different entities from government, to school districts, insurance companies and industry to overcome the limits that we have now in dealing with these endemic problems.
Host: Wow, that's amazing. I want to thank you so much for your time today. We appreciate all you do and the amazing impact you are having on the health of children and their families.
Dr. Huang: Thank you very much, Jan, and it was a pleasure to be here with you.
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