This week, I sat down with Ascanio Guarini ’16, an Honors engineering and economics major, to discuss biomedical research he did over the summer of 2014 at a lab affiliated with Massachusetts General Hospital.
When Guarini joined the lab, the team was developing a new technology to combat esophageal lesions that are a precursor to throat cancer. These lesions, which result in a condition called Barrett’s esophagus, are usually caused by acid reflux. If undetected or untreated, Barrett’s esophagus, which can be considered stage 0 esophageal cancer, will develop into adenocarcinoma (a nasty cancer). Once it has progressed past stage 0, esophageal cancer usually requires surgery, and still only has a 5-year survival rate of about 20%1. Fortunately, at the time Barrett’s esophagus is detected, the lesions are only growing on the mucosal lining of the esophagus. If the abnormal cells of the lining can be destroyed without causing damage to the rest of the esophageal wall, the progression to esophageal cancer can be halted. However, currently available technologies that do this are spotty: they burn away the mucosal tissue, but often are too superficial and leave some precancerous cells behind in deeper layers of the lining. On the flip side, they can also burn away too much tissue, causing serious damage to the healthy esophageal wall and requiring, as Guarini described it, “gruesome” surgery.
When Guarini arrived for the summer, the lab was in the development phase for an ingenious device that took advantage of the elastic characteristic of the mucosal lining, which is stretchy like skin. As Guarini explained, the device “[uses] a vacuum to suck the lesioned tissue away, isolate it, and then burn that tissue away specifically.” Picture putting your skin up against a vacuum. The vacuum pulls your skin out, but your muscles, bones, and everything else stay in place. That’s what the device does to the mucosal lining. Another useful thing about the device is that it’s shaped like a cylinder, with the vacuum going 360º around it, and can be moved up and down to ablate the entire esophageal lining as it goes. “Imagine you’re shaving away a layer of tissue. You put this catheter in, have this device set up, and you can go up the esophagus and ablate away,” explained Guarini. Because the device can so specifically target the tissue, it would theoretically only require one treatment, as opposed to current methods that require up to three sessions over nine months, with healing periods in between.
What was Guarini’s role in all of this? “Before we go into in vitro studies on animals, we want to know if we need to change anything about the design,” he clarified. “So I had to develop, essentially, a computer model of this device from scratch. I started from, OK, I have the dimensions of this device, and I have this package in MatLab … where you can do a lot of really good modeling.” Guarini essentially needed to figure out the numbers behind the design — how much heat did it need to emit to destroy all the lining tissue of the mucosal lining, but not cause extraneous damage? How fast could the device be moved up the esophagus while still destroying all the targeted tissue and leaving no lesions behind? How much electrical power would this all take, and was that a realistic amount?
“The results were pretty cool,” said Guarini. They modeled the device with varying speeds (between 1 mm/sec at the slowest and 26 mm/sec at the fastest) and at varying temperatures, and found that above 70º Celsius (158º Fahrenheit), speed had little effect on the efficacy of tissue destruction. That is, they could move the device very quickly, and it would still be hot enough to destroy all of the targeted tissue. At 70º Celsius or below, the model predicted that the device would need to move more slowly to effectively kill all of the lining.
“It was kind of surprising how perfect it was, right, and that’s kind of a concern in the sense that… is that actually the device, or is that the model? And that’s something I couldn’t actually test,” Guarini expanded. They would need to experiment on cadaver tissue in order to ascertain exactly how accurate the model is, he said, which is what the lab is currently working on.
“It looks like we need a pretty high temperature, probably like 80º,” Guarini said. The model predicted no danger to deeper tissues even at 90º, but Guarini thinks it’s possible that the model may not be fully accurate in predicting the level of damage. “90º is pretty hot, and you may actually go deeper and do more damage than the model is predicting,” he explained.
Guarini also found the power requirements were realistic — at high temperatures, about 18 watts. That’s less than the power that a typical light bulb uses.
Ultimately, Guarini said, the lab would also apply imaging techniques to the device, so that they could monitor the ablation of the tissue in real time and make sure everything was working the way they wanted it to.
Guarini found it fascinating to see the way the lab, which is based in academia rather than for profit, worked from bench to patient. “This is maybe my romantic view of it, but [they] make something that can make a difference, achieve a solution to a significant problem that’s better than what’s available, and then have those that have the resources and the marketing power, business power, bring it to the patient. It was definitely cool to see the process in general,” he said.
Guarini said he feels a pull toward understanding systems on all levels, from “a small scale engineering system like this device to an incredibly large complex system like healthcare.” Being part of this project was exciting for him, he said, but he also wants to expand his horizons to a more macroscopic systems view. Guarini knows that next year, he’ll be at Stanford, doing big data applications in health policy research. Guarini believes this research will enable him to apply his majors in economics and engineering, as it is at the intersection of health economics and policy evaluation. He hopes that next year will give him an idea of a larger scale system that he might be interested in, and beyond that, he’s not sure what he will do. For Guarini, his education has taught him to find his interests, and it’s been a long searching process: “What are the kind of problems I want to solve, and what kinds of problems match my skills, and at what scale do I want to solve them?”
Guarini described his participation in the project as fulfilling. “In 5 to 10 years, if this device ever comes to market, I can say, OK, I worked on that, I had a piece in that project,” he said. “And obviously I take next to no credit for it because relative to the work that they do I hardly did anything. But I did have a piece, a small contribution, and that was an amazing aspect of being a part of that.”
For more information, check out the Vakoc lab website: http://vakoclab.mgh.harvard.edu/