1. Neff Newitt, Valerie

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Eugene K. Lee, MD, Associate Professor and Division Director of Urologic Oncology for the Department of Urology at the University of Kansas School of Medicine, claims his "personality is well-suited to urologic oncology."

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Hmmm, really? That would beg the question: What kind of personality traits shout urology?


"I find people in urology are affable. Because there are fewer emergencies in urology, people in this specialty actually DO get some sleep at night. They are typically friendly. I've had mentors who not only are phenomenal surgeons and teachers and scientists, but they're also fantastic family people, too. I'd see them around their kids and spouses and I'd see that their families actually know them and LIKE them. That was important for me, because my family is my entire life," said Lee.


He quickly expanded that proclamation to admit there is yet another driving passion in his world: research and clinical work focusing on bladder cancer. Lee has already delivered impressive findings related to diet and cancer cell production, as well as care management after cystectomy using an innovative app he helped design.


Born in a Chicago suburb to immigrant parents from South Korea, Lee moved with his family to Kansas City when he was 7. "That's where I've stayed. I did all of my training here, other than my urologic oncology fellowship at MD Anderson in Houston," said Lee, crediting family interactions for his earliest interest in medicine. "I initially learned the importance of medicine from my mom, a pharmacist." Coincidentally, Lee is married to a pharmacist, Krista, with whom he has a young son and daughter, Gavin and Ava.


Further influenced by his older sister, a physician, and his brother-in-law, a surgical oncologist, Lee homed in on a career in surgery. "I always knew I wanted to operate in the abdomen and the pelvis, and so that led me to urology. It suited my personality; that is where I fit."

Eugene K. Lee, MD. E... - Click to enlarge in new windowEugene K. Lee, MD. Eugene K. Lee, MD

There was an extremely personal influence, too, that positioned Lee to pursue oncology. "When I was in medical school, my father was diagnosed with acute myeloid leukemia. He struggled and battled through it. Observing the ordeal he was going through, and seeing the level of expertise and care he received [at Mass General Hospital] was just incredible. That solidified a desire to work in oncology."


Great mentors also figure largely in Lee's expanding professional tapestry. "My current chair, Jeff Holzbeierlein, MD, [Chair of the Department of Urology at the University of Kansas Medical Center], has been a mentor since I was a medical student. I watched him and loved what he did-a lot of research and bladder cancer clinical work as well. That influenced me, so I spent 2 years in the Bladder Cancer Laboratory at MD Anderson, honing my skills in terms of research and trying to balance my practice between the research aspects of translational science and a busy clinical schedule."


Research Interests

When he was still a fellow, Lee became interested in the intersection of diet, exercise, and health. More specifically, he began to consider the relationship of glucose metabolism and bladder cancer.


"I started looking at the literature critically in terms of calorie restriction versus carbohydrate restriction versus glucose restriction. It led me to explore that as a field," said Lee. "As soon as I got to KU as staff, I applied for small pilot awards to begin preliminary studies. Often, physician scientists observe patients from their own practices and consider some of the outliers. I had two patients in particular, both of whom had very poorly controlled diabetes, and cancer recurrences extremely quickly after bladder cancer resection. I thought, 'There's got to be a link here.'


"So I started out with some lab work, looked at some of the literature. As I started to do some cell culture, typical different exposures to the cells with increasing and decreasing levels of glucose, I saw what happens to the cells and the inner workings of it."


Lee and his team focused on an enzyme, pyruvate kinase (PKM2), which has been well-studied in many different cancer systems. "We explored it in bladder cancer and found the enzyme goes back and forth between a tetramer and a dimer. Essentially, there's an active and inactive form that is higher and lower in cancers," explained Lee. "We were able to show that increasing and decreasing levels of glucose actually move the enzyme from an active to inactive state, which may be a source of helping cancer cells proliferate."


Further, the team was able to demonstrate the use of drugs to enable that back-and-forth switch, and show that cancer cells grow slower when the switch is accomplished.


"We were also able to find a kit that was used in colon cancer in stool. It is typically used to look at this enzyme in fecal matter and in plasma. But we thought to ourselves, 'Why couldn't we use this in urine?' The holy grail of bladder cancer is to be able to detect cancer or stage based on urine, as opposed to how we do it now by cystoscopy, where we take a scope and place it into the bladder and take a look around, which is very uncomfortable for patients," said Lee.


"We found the PKM2 enzyme is higher in patients with bladder cancers, as opposed to normal controls. We started looking at tissues and cell culture and have started work to potentially use it as a diagnostic marker."


Feasibility Trial

Lee also conducted a pilot clinical trial examining diet, exercise, and lifestyle in respect to cancer. "We recruited patients who had diabetes or pre-diabetes and put them on a strict carbohydrate-restricted diet, below 130 grams per day, which is based on diabetes literature. For the purposes of this trial, we emphasized reducing starchy carbohydrates," said Lee. "I have a hard time telling people to limit fruits and vegetables. I think there are certainly better fruits than others; blueberries, raspberries, and blackberries are especially good."


Because this was a feasibility trial, it wasn't to see if there was an end point. "Rather, it was to say, 'We have patients with bladder cancer and diabetes. If we try to do a really intensive trial of carbohydrate restriction and try to decrease blood sugars and urinary glucose, will patients actually stick with the diet?' This is an important first step because there's no point in doing a huge randomized trial if patients aren't going to stick with the protocol. What we found is that patients actually will stick with it, and their glucose is decreased, and their blood and urine insulin levels are decreased. All of the things that we thought would move in the right direction actually did."


Lee mentioned that exercise was also recommended to patients. "It all goes together. When it comes purely to weight loss, the literature is pretty sound that diet is more important than exercise. But exercise is important to build and maintain heart health, lung health, and muscle health. We've also found that exercise actually improves insulin numbers, which in turn helps with glucose levels."


Managing Post-Cystectomy Care

Another area of Lee's work involves the development of a tablet-based app, which he has already trialed.


"For bladder cancer patients, especially advanced bladder cancer, the gold standard treatment for muscle-invasive disease or recurring disease is to remove the bladder. In men, it's the bladder and the prostate. In women, it's the bladder and basically a hysterectomy. Then we must build a urinary diversion. It's a complicated operation, and these patients, at baseline, just don't do very well," said Lee.


"I tell my patients it's a three-part operation. You remove organs, you remove lymph nodes, and then you construct a way for the urine to exit the body," Lee continued. "The complication rate is actually 60-65 percent. Some 20-25 percent have high-grade complications, and there is about a 5-7 percent mortality rate at 90 days."


The reason for such dim expectations is found in the fact that the number one cause of bladder cancer is smoking.


"Often these patients are older smokers who not only have bladder cancer, but also have lung disease, heart disease, and vascular disease. Then we put them through a huge trauma, like a radical cystectomy, and it's a lot to take on. We can do a urinary diversion through an ileal conduit, which is like an ostomy for urine, or a neobladder, where we take a longer segment of bowel, create a pouch out of it, put it where the bladder used to be, and reconnect everything. It all represents a huge lifestyle change for these patients, with a lot of education required."


Lee decided to develop an app to help patients learn to better manage post-surgery care and recovery.


"We created the app for the following reasons. First, we wanted to deliver information to patients in a timed-release program. People come into the doctor's office and they're shocked and scared. All of the information we're trying to relate to patients in a 20- to 30-minute visit just isn't going to sink in," said Lee.


"So we created videos on different sections and parts of the radical cystectomy and education pertaining to different ways we can take the bladder out, managing ostomies, what the postoperative course will look like, and the possible risks. Instead of giving all of that information at once, at 21 days before surgery a patient gets a couple of videos to watch through the app, then at 14 days before, a couple more videos. They are bite-sized pieces of information. They can watch and share with family members, so everybody is on board and learning about the radical cystectomy."


The second reason for the app was for improved monitoring. "We encourage patients to walk, and walk, and walk," Lee stressed. "We gave each of them an accelerometer. We said, 'We want you to have X number of steps before surgery, leading up to surgery, and then after surgery. Walking helps with bowel function, maintains muscle mass, pumps blood, and decreases inflammatory factors. Some literature says if you walk, your bowel functions quickly; that's really important because bowels 'falling asleep' is one of the common causes of longer hospital stays."


Lastly, the app allows patients' medical teams to monitor their vitals. "When patients go home, we want to know about any abnormalities prior to them having to call us because of something emergent," said Lee. "As I mentioned before, 65 percent of these patients will have a complication; a lot of them are infectious. Seeing their vitals on a daily basis, we can observe if their temperatures are going up, or their heart rates are going up a little bit. Patients may not necessarily feel bad yet, but we may be able to identify infections early on. We're able to interact with patients in a more timely fashion. The patients were really enthusiastic about the app, because they were able to take more ownership of their care and feel more in control of their care. Patients want that."


The app is now moving toward a randomized clinical trial being designed to compare routine standard of care to care enhanced with the app. "We want to monitor patients to see whether or not the app usage actually moves the needle in identifying complications earlier, and helps patients do better," said Lee.


As he considered what his future work might encompass, Lee spoke of his desire to embrace a science-based holistic approach to patient care.


"I have some ideas I'm pursuing. I think there are definitely some patients who influence their own care, outlooks, and outcomes. But what we don't know is how resilient they really are. How vigorously do they bounce back from trauma? I think that can be predictive. This is something I'd like to explore next," he noted.


"Sometimes we go to oncology meetings and we discuss the minutia of surgical technique, and of course there is a lot of importance to it. But I think we sometimes lose sight of some of the other factors that we should focus on, such as nutrition and a patient's mental makeup. We sometimes miss an opportunity to really talk to patients about healthy living. There's good science in meditation, for example, and there's good science in other factors that also play a role in how well a patient will do," said Lee.


"When patients are diagnosed with cancer it becomes a great window of opportunity for us to talk to them about lifestyle modification. Oftentimes, in the clinic I say, 'I bet you didn't think you were going to talk this much about fruit with your urologist.' But that's where we do need to place at least some focus in our care."


Valerie Neff Newitt is a contributing writer.


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