Asking Questions, Finding Answers

When Kelly M. McMasters, M.D., Ph.D., trained in the General Surgery Residency Program at U of L, then-chief resident Michael Edwards, M.D., knew "he'd be someone special."__Edwards, now chairman of the Department of Surgery at the University of Arkansas, saw his prediction come true in 1996, when McMasters returned to the University of Louisville as an assistant professor of surgical oncology and rapidly began climbing the academic ranks.

After a mere seven years at the university, McMasters, the Sam and Lolita Weakley Professor of Surgical Oncology and director of the Division of Surgical Oncology, has overseen the development of the multi-million-dollar Surgical Oncology Clinical Research Center.

The center collects and houses data from more than 12,000 patients involved in a variety of studies, including groundbreaking research directed by McMasters in the treatment of melanoma, breast cancer and liver tumors.

"Kelly has had his eye on the target all along," says Hiram C. Polk, M.D., chairman of the surgery department at U of L and McMasters' mentor since his days as a surgical resident here. "He has developed a good lab, an excellent program of clinical research, provides excellent patient care and has helped build the division through the recruitment of talented professors."

McMasters graduated from the M.D./Ph.D. program at the University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, earning a Ph.D. in cell and developmental biology from Rutgers University before completing his surgical residency in Louisville.

"I chose the University of Louisville for my residency because of Dr. Polk's reputation as an international leader in surgery," McMasters recalls.

He credits his training under Polk, and Polk's support, as key factors in his success since.

The lessons McMasters learned from Polk influenced his approach to patient care, research and education.

"Dr. Polk demands excellence in trainees and gets what he asks for," McMasters says. "I learned early on that I needed to communicate effectively, be able to justify my decisions and make good decisions."

McMasters also embraced Polk's example of the "surgical conscience."

"This is the notion that a surgeon is ultimately responsible for a patient's care," McMasters explains. "This means being readily available, taking the time to make the rounds and not letting details slip through the cracks."

After a fellowship at the University of Texas-M.D. Anderson Cancer Center in Houston, McMasters decided to return to Louisville to work with his mentor.

"I came back to the university because of Dr. Polk," McMasters says. "He's made sure I had everything I need to be successful here -- an environment with basic science lab opportunities and the ability to develop a program in clinical research, recruit the best people and build the program.

"A lot of credit also goes to Drs. Sam and Lolita Weakley. They were incredibly generous in endowing the professorship that I hold, and any success that I've enjoyed is a direct result of their support."

Cornerstone of Research

McMasters' work serves as the cornerstone of the clinical research program.

Perhaps his best-known project is the Sunbelt Melanoma Trial, the world's largest study of melanoma, started in 1996. McMasters is the principal investigator in the nationwide study involving more than 3,500 patients and 79 centers across the United States and Canada.

Participating patients undergo sentinel node biopsy, which involves the removal of the sentinel lymph node -- the first to which cancer would spread -- to determine if skin cancer has invaded the lymphatic system. The process is less invasive and has fewer side effects than the traditional removal of multiple nodes.

The procedure is precise enough that doctors can find one melanoma cell among 1 million normal lymph node cells, McMasters says. If melanoma is not detected in the sentinel node, patients are monitored for recurrence of the disease. If melanoma is discovered, surgeons remove the surrounding lymph nodes.

Following lymph node removal, a select number of patients receive the drug interferon alpha-2B, which is effective in treating certain cancers but also can have undesirable side effects.

"The process helps us determine who needs interferon and who does not," McMasters says. "The bottom line is better treatment of melanoma."

McMasters also directs the University of Louisville Breast Cancer Sentinel Lymph Node Study, employing the same sentinel lymph node biopsy technique as the Sunbelt Trial to determine if breast cancer has spread to the lymph nodes.

The study has gathered data from more than 4,000 patients and more than 300 surgeons around the United States. It is the largest study of its kind, representing more than half the world's data on sentinel node biopsy.

"In the past, we took out all the lymph nodes under the arm, which sometimes caused permanent swelling of the arm, called lymphedema," McMasters says. "Now, patients go home the same day as their surgeries and have fewer complications. The study has helped change the standard of care for breast cancer patients around the world."

In addition, McMasters directs the multi-center study of a technique called radiofrequency ablation, making the University of Louisville/Norton Hospital one of the first centers in the country to perform the procedure on liver tumors.

The process is relatively simple: A probe is inserted into the tumor and microwave energy is applied, killing the cancerous cells in as little as 15 minutes.

"Some patients have tumors that can't be resected," McMasters explains. "This technology allows us to treat more patients, extend their lives by a factor of two or three, and even re-treat some patients with liver cancer."

There are other benefits, too. For example, McMasters says the procedure often is performed in a minimally invasive fashion. That means patients can go home after just one night in the hospital, wearing a simple adhesive bandage to cover the small incision.

Gene therapy is yet another field in which McMasters is conducting oncology research, serving as the director of a National Institutes of Health-funded laboratory that examines potential genetic targets. Working with Sam Zhou, Ph.D., McMasters has explored the use of viruses to deliver genes that kill _cancer cells.

In September 2002, he was awarded a $1 million, four-year grant from the NIH to continue the study of cancer gene therapy.

Asking Questions

Despite his impressive accomplishments, McMasters says he's more interested in the pursuit of knowledge than personal recognition.

"I started off with an interest in research," he says. "My training and background has stimulated me to ask questions and try to answer them."

Surgery, to which McMasters was drawn because of his desire for a "definite, concrete outcome to improve the patient's well-being," serves as the perfect complement to the more academic pursuits of research.

Already, he has begun to see positive results from some of his investigations.

Early on, some women in the Sentinel Node Breast Cancer Study agreed to have their lymph nodes removed to make sure the sentinel node biopsy readings were accurate, despite the potential for painful side effects.

One woman, a factory worker in her late 30s who was accompanied by her sister-in-law, suffered chronic arm swelling that continues today. Later, the sister-in-law was diagnosed with breast cancer and underwent sentinel node biopsy. She went home the same day and resumed normal activity.

"Because of the courage of the women who took part in the research, real progress has been made," McMasters says.

His work also has made an impact on the department as a whole. McMasters is proud of the "exciting progress" the department is experiencing as the result of increased interest in research.

"We have lots of people engaged in research on many different fronts. We have people who are every bit as good as those you'd find at Johns Hopkins, M.D. Anderson and Memorial Sloan-Kettering. We try to create an environment where people are always asking important questions and finding the best ways to answer those questions."

Polk says the program is a magnet that draws residents interested in research opportunities.

"What is telling is how often people have chosen Kelly as a role model to work alongside," Polk notes.

But research is just one part of his daily routine, and McMasters draws on extraordinary organizational skills to juggle the demands of his position, Polk says.

"He has a major practice of the most complicated cases, an NIH-funded research program which is highly productive, conducts the largest melanoma trial in history and still teaches and fulfills his duties as a faculty member," Polk says.

McMaster's downtime is spent with his wife, Beth, an attorney, and sons Austin, 10, Steven, 8, and Owen, 4.

Not content to rest on his laurels, McMasters wants to reinforce the department's focus on clinical care as well as research and continue recruiting outstanding doctors to build existing programs.

Polk looks forward to McMasters' next move, reveling in the success of his protégé.

"It has been fun to watch him grow, take every step of added responsibility and shine at every level," Polk says.

Edwards sees the division's rise to prominence as the result of a wonderful collaboration between Polk and McMasters.

"Hiram has something that just causes people to aspire to fulfill their greatest potential and pursue their honorable mission in life," he says. "Kelly is as good an example of that as anyone."