C Stands for Care

Stomach and colorectal cancer that has spread to the liver are complex, challenging illnesses. Surgical specialists are leading research to redefine “best” in the provision of care for patients with these and related diseases

Illustration of colorectal cancer suffering

Each year, Canadians walk, bike, run or hold other activities and events to raise money to fund research into common cancers such as breast and prostate. While these are important pursuits that garner a great deal of public attention and support, many researchers are working under the radar to study lower-profile, but potentially more deadly, forms of cancer. Colorectal cancer that has progressed to the liver, for example, is an advanced-stage and serious form of cancer, and while stomach cancer rates are lower in Canada than in many other countries, a high percentage of patients diagnosed with it will die.

Two surgeon-scientists at Sunnybrook Research Institute’s Odette Cancer Research Program, Dr. Paul Karanicolas and Dr. Natalie Coburn, are part of teams studying these cancers of the gastrointestinal tract. Karanicolas allocates about 75% of his time to conducting research and 25% to treating patients. “Although much of my work is spent on research, I’m a surgeon and clinician first,” he says. “That means my first dedication is to my patients.” That dedication helped Karanicolas identify a need in the patients on whom he was performing liver surgery, often for colorectal cancer that had spread there. He noticed that a number of them who were treated for pain control after surgery were suffering unpleasant side effects that were slowing their recovery. “That moved me to want to find a better way to administer pain control,” he says.

There are two methods of relieving pain following liver surgery. The first is intravenous (IV) medication such as morphine, the amount of which the patient controls; the second is an epidural catheter that is put into the patient’s back before the operation to freeze from the lower rib cage downward, then removed three or four days post-surgery. Both methods have drawbacks that delay recovery. With the IV, they include trouble breathing, slowed bowel function and drowsiness, which makes it harder for patients to get out of bed. Those who receive the epidural may experience discomfort when the catheter is inserted, limited mobility after the operation, lowered blood pressure causing dizziness and, although it’s rare, bleeding around the spinal cord that can cause leg paralysis.

Karanicolas and a team of surgeons, anesthesiologists, nurses and others at Sunnybrook Health Sciences Centre and Toronto General Hospital have developed a technique to improve pain-medication delivery called MOTAP catheter placement. (MOTAP stands for medial open transversus abdominis plane.) With MOTAP, the surgeon places one or two catheters that deliver pain medication directly through the open surgical site where pain nerves are found. “The catheters are inserted in less than five minutes at the end of an operation without any discomfort to patients and are easy to remove,” says Karanicolas. “And they carry no risk of bleeding or spinal cord injury.”

Dr. Paul Karanicolas

Surgeon-scientist Dr. Paul Karanicolas is leading multisite clinical trials to advance care of people who undergo liver surgery, often for colorectal cancer that has spread to this vital organ.

Photo: Doug Nicholson

Karanicolas is the study’s co-leader and the site leader of the blinded, randomized controlled trial to assess the MOTAP catheters, which began in the fall of 2013. By the end of 2014, about 60 patients will have been enrolled at each site, and the team plans to submit its findings in the spring of 2015.

If that wasn’t enough to keep Karanicolas busy, he’s also the study and site leader for a clinical trial that will evaluate the impact of tranexamic acid (TXA) on blood transfusions in patients undergoing major liver resection, during which part of the liver is removed. Blood loss is a major risk during this type of surgery. Tranexamic acid is a drug that stops the breakdown of blood clots during or after surgery; it’s often used in other medical situations, but rarely in liver surgery, because there is no strong evidence that it reduces bleeding.

“That’s what this trial will aim to find out,” says Karanicolas, who is also an assistant professor at the University of Toronto. “If we were able to demonstrate that tranexamic acid used in major liver resections resulted in a significant decrease in blood transfusions, clinical practice worldwide would be likely to change.” In Canada alone, more than 2,000 patients undergo liver resection every year, about one-third of whom require blood transfusions during or after surgery. The transfusions are scarce and expensive, plus they can increase the chance of infections, heart complications and breathing problems. There’s also a higher risk of the cancer returning in patients who have received blood transfusions.

The TXA trial will be done in two phases. The results of the first phase, which is monitoring 20 liver-resection patients, should be ready by the end of 2014; the second phase will begin in September and assess another 1,000 patients across Canada.

In addition to researchers from Sunnybrook, the multidisciplinary team hails from McGill University Health Centre in Montreal, Foothills Medical Centre in Calgary, University Health Network in Toronto and Queen Elizabeth Health Sciences Centre in Halifax.

Karanicolas enjoys the collaborative nature of the research. “It’s a unique opportunity within both Toronto and Canada to work with different organizations and disciplines to help our patients,” he says. “Everyone’s role is instrumental. As for me, I’ve always wanted to treat patients and advance knowledge—it’s the optimal combination. I’m most passionate about using research to answer medical questions. It’s about taking information from the bedside to the bench, and then back to the bedside.”

A Gut Feeling, Grounded in Science

Coburn is also doing groundbreaking work. She leads a team studying the best treatment options for patients with gastric cancer. Although this disease is fairly rare in North America compared to other countries, it’s responsible for 10% of all cancer deaths worldwide. Despite five-year survival rates of 40% to 60% in advanced gastric cancer patients in Asia and Europe, the five-year survival rate for similar cases in North America is around 30%. Although the theory has been that improving the treatment these patients receive would improve survival rates, few studies had examined the effect of care processes in the outcomes of patients with gastric cancer.

Coburn, who is head of the division of general surgery at Sunnybrook, developed an interest in this area of research when she was a resident at an American hospital. “I was concerned about the quality of surgery that gastric cancer patients received in a few cases I observed there,” she says. In earlier work, she found that despite the evidence of an improved chance of survival when gastric cancer patients have surgery combined with either chemotherapy or chemotherapy and radiation, many patients don’t receive appropriate treatment, with up to 43% having surgery alone, and less than one-third having appropriate staging of lymph nodes. Because surgeons in Western countries like Canada and the United States treat so few patients with gastric cancer, lack of experience may contribute to deciding on the best treatment plans.

To address this, Coburn, who is also an associate professor at U of T, led a RAND/UCLA appropriateness study to help establish the highest quality processes of care for these patients. This is a method that, as the RAND manual says, pools the “best available scientific evidence with the collective judgment of experts to yield a statement regarding the appropriateness of performing a procedure at the level of patient-specific symptoms, medical history and test results.”

A panel of 16 physicians with gastric cancer expertise was assembled from six countries; they met in Toronto in October 2010. One thing they agreed on was that the best care for patients is in the setting of a multidisciplinary team, including surgeons, medical oncologists, radiation oncologists and nutritionists. They also felt strongly that those with metastatic gastric cancer and no symptoms are likely not helped by surgery—in those patients, who all have a short life expectancy, chemotherapy might offer a better quality of life.

Coburn says the importance of the expert panel was the influence of those outside North America. “We need to respect the work that has been performed in Japan, Korea and other Asian countries, where gastric cancer is more prevalent.”

Coburn treats complex gastrointestinal cancers, including those of the stomach, pancreas and liver. “My theory is that if you do all the small steps well, you end up with better outcomes,” she says. Those small steps include removing tumours with appropriately large margins of cancer-free tissue and removing enough lymph nodes to examine them for more cancer, then deciding with the patient’s input on the best course of treatment.

Dr. Natalie Coburn operates

Dr. Natalie Coburn operates on a patient with gastric cancer, a disease that was responsible for 2,000 deaths in Canada last year. Her research seeks to improve outcomes for these patients.

Photo: Doug Nicholson

“With most cancers, surgery isn’t enough to kill the cancer unless it’s caught at an early stage,” says Coburn. “When the cancer is more advanced, patients typically need surgery plus treatment following the surgery. But some patients, especially elderly ones, may decline the additional treatment because the chemotherapy drugs are toxic and hard to tolerate. Each treatment needs to be tailored to the patient.”

Further study into optimal treatment, as well as new chemotherapies, is required. “Gastric cancer is a disease that desperately needs better drugs,” says Coburn. The study team has been awarded a Canadian Institutes of Health Research grant to allow the researchers to determine how much it will cost to provide optimal treatments to patients. Next steps include working with Cancer Care Ontario to translate the research findings into treatment guidelines; if all goes well, the guidelines should be ready to roll out by the end of 2014.

In the meantime, Coburn will continue striving to offer the best possible care to her own gastric cancer patients. “Patients need a team of doctors and other health care providers, not just the surgeon, to help take care of them through what is a difficult, complex cancer,” says Coburn. “For surgeons, treating one or two of these cases a year isn’t enough to learn about the nuances of care. You want to know that everything possible has been done, and done appropriately, for each patient—then we’ve done the best we can.”

The Canadian Cancer Society, and the Ontario Ministry of Health and Long-Term Care provided support for Coburn’s work on the RAND/UCLA study.

For Karanicolas, the Canadian Institutes of Health Research is funding the TXA trial; the provincial AFP Innovation Fund is funding the MOTAP catheter trial.

Dr. Paul Karanicolas
Dr. Natalie Coburn