"I always say to patients that the only thing worse than having cancer once is having it come back after surgery," said Benjamin D. Shogan, MD, Assistant Professor of Surgery at the University of Chicago. So in his active research lab, this surgeon scientist, specializing in colon and rectal cancer, inflammatory bowel disease, diverticulitis and anorectal disease, is looking for novel strategies to help patients avoid such a recurrence.
Specifically, he is looking at how the environment of cancer influences its recurrence, and whether the identification and manipulation of various bacteria may lead to fewer postoperative complications and improved outcomes.
A native of the Princeton, NJ, area, Shogan came to his interest in medicine by watching the once popular TV series ER and the raucous and dramatic medical interventions it portrayed.
"When I entered New Jersey Medical School, I wanted to be a trauma surgeon," he recalled. "I liked the hype, and rush-rush-rush fast pace. But when I did my residency at the University of Chicago, I found I enjoyed the relationship with patients that were made before surgery. That fast pace became less exciting than the meticulous planning of a surgery, the removal of a cancer, and seeing a patient recover afterward. That became more exciting, and my true focus."
Married to a pediatric ENT surgeon and father to three young children, Shogan has built upon and expanded research which he first began during his residency.
"I was interested in learning how intestinal bacteria can influence healing of the colon. Think of the colon as one long pipe. When we do surgery, we obviously cut out the bad piece, whether from cancer or diverticulitis, and then tie the two ends together. And just like plumbing, you want it to form a watertight seal. But what we found in our research is that bacteria present at the time of surgery can influence the healing and can cause the 'pipe' to become leaky. If that happens, the patient can become really sick," he explained. "So we started working in animals-mice and rats-and now we're moving on to studying bacteria in humans."
The Role of Bacteria in Recurrence
Identifying bacteria that cause the "leak" is only the beginning. "We do not think it's just one bacterium. When you're growing your lawn, you don't have just one type of weed. There are many. But the inverse side of that example is that if you have a really nice, thick lawn, it might prevent those weeds from growing at all. So we're looking at both sides, in terms of human gut bacteria. Once we identify influential bacteria, we are exploring how, at the time of surgery, they can influence cancer recurring after the cancer has been cut out.
"Our research has found that if we do surgery in mice that mimics the surgery we do in humans with colon cancer, we can have cancer recur, but only under certain environments where certain bacteria are present. These bacteria make an enzyme called collagenase, which can break down products within the bowel wall that tend to promote the cancer, and potentially help cancer cells escape that environment, forming a recurrence.
"So, in short, what we think is happening is that the bacteria in the colon at the time of surgery can influence cells that are exfoliated from the primary tumor, and we find them a couple of years later as a recurrence."
Shogan said that, once influential bacteria are identified and their capability to promote cancer is understood, "...then we can try to prevent the presence of those bacteria before surgery. It also could be that, if those bacteria are present beforehand, they are promoting metastasis, even before surgery."
Evolution of Bacteria
Another interesting aspect to the research is found in considering what happens to the bacteria and, in response, the patient.
"Surgery, in itself, dramatically changes the bacteria," declared Shogan. "Think about it: Bacteria are living in the colon and then you take them into the operating room. You open up the colon, you put your hands on it and tie the two ends together. It's like an earthquake for the bacteria. It's not just the bacteria that were there before you opened up the patient, but it's the bacteria evolution after you've opened the patient that might be most important."
Shogan's lab is now collecting stool samples from patients before and after surgery to see if findings in the lab correlate to humans. If the researchers' hunches are correct, successful cancer treatment of the future could be informed and aided by an examination of a patient's gut bacteria.
"Right now, when a patient gets diagnosed with colon cancer, we look at certain factors of the colon cancer, such as how deeply it invades into the colon wall, and if lymph nodes are positive or not. But we don't really take into account the environment that the cancer is in," said Shogan.
"So I can foresee that in the future not only will we look at those factors of the cancer itself, but also the factors of the environment, one of which will be the type of bacteria present. We just don't know yet exactly what those environments are, but I think this research will better define that. And hopefully we'll be able to change that environment, to make even a 'bad' cancer in a good environment less dangerous."
While the idea of examining the microbiome and its correlation to cancer is a "hot topic" pursued by various researchers, Shogan and team are distinguished in the fact that they are all surgeons.
"We're not cellular biologists trying to figure out the next chemotherapy," said Shogan. "We are trying to figure out, while we do surgery on a patient, how to prevent their cancer from coming back. I think that is a bit of newer-and unique-view.
"One day down the line, perhaps 50 years from now, we'll figure out how to prevent cancer from occurring at all. Patients might not even need surgery by then. But until that happens, a lot of people go through surgery and, unfortunately, too many people have their cancer recur. We try and use our experience that we've seen in patients with cancer to mimic it in animals, and then see if we can translate that into new ways to help our patients."
Valerie Neff Newitt is a contributing writer.
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