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OneThousandOne represents the amount of time, verbally, that it takes to count to one second. In this one second of time, a great thing happened at Nebraska Medicine. In fact, several great things probably happened. A patient was cured, a researcher found the missing link, a nurse treated an injury, a doctor comforted a family or maybe a child just smiled.
MOMENTS IN MEDICINE
Spring | Summer 2011

108 Degrees

Surgeons at The Nebraska Medical Center have added a new weapon in their battle against cancer — heat. Heat by itself kills cancer cells. Heat of 108 degrees or more, combined with chemotherapy, amplifies chemo’s effectiveness and adds another mechanism to induce cancer cell death.

Steve Shufelberger

There are some things you just know when it’s right... like when you look at a freshly painted room for the first time. The first time you try on a new pair of jeans. Or that first bite of chocolate cake.

When Steve Shufelberger walked into the office of Jason Foster, MD, for the first time, within seconds he knew that he was the right doctor. Dr. Foster was a man he could trust, says Shufelberger.

This was important. Shufelberger was about to put his future into the hands of Dr. Foster, a surgical oncologist at The Nebraska Medical Center. Diagnosed with abdominal cancer just a few weeks earlier, Shufelberger was meeting with Dr. Foster to discuss a new and innovative therapy for treating cancers in the abdominal cavity called hot chemo. While Shufelberger had never heard of the treatment technique before, it was an approach Dr. Foster assured him would provide the best results with the least down time.

The treatment involves surgical cytoreduction (CRS), also known as tumor debulking (removal of a tumor). This is performed in conjunction with hyperthermic intraperitoneal chemotherapy (HIPEC), also called hot chemo. Dr. Foster is one of a very small number of surgical oncologists in the United States practicing this technique and has been performing the procedure for about eight years. He received special training in this technique during his surgical oncology fellowship at Roswell Park Cancer Institute in Buffalo, N.Y. Prior to his fellowship, he completed surgical training at Case Western Reserve University/University Hospital of Cleveland in Ohio; and, he received his medical degree from Temple University School of Medicine in Philadelphia, Penn.

Hot chemo (HIPEC) involves instilling a heated solution of chemotherapy in the abdominal cavity to kill any remaining small tumor nodules and microscopic cells, which typically remain after cancers have been removed from the
abdominal area.

This approach is used for cancers that originate or have metastasized to the abdominal (peritoneal) cavity, notes Dr. Foster. The most common form of cancer metastasis involves the spreading of cancer through the bloodstream and lymph nodes to distant organs like the liver, lung or brain.

Jason Foster, MD
Jason Foster, MD

Another form of metastasis is dissemination of cancer in the abdominal cavity that houses the gastrointestinal (GI) and genitourinary (GU) tract. This type of metastasis occurs when a tumor arising from the GI or GU tract grows large enough to rupture the capsule or outer lining of the organ. Microscopic cells spill into the peritoneal cavity, which can then spread and grow on the surface of other intra-abdominal organs.

“A simple analogy would be spilling rice in the kitchen of our home,” explains Dr. Foster. “Later, we may find rice kernels in other rooms of the house.” This type of spreading is called carcinomatosis and commonly includes cancers that originate from the colon, stomach, appendix, small intestine, ovary, pancreas, carcinoid and pseudomyxoma peritonei. Occasionally cancers can originate outside the abdominal cavity, such as breast cancer, and can cause carcinomatosis through lymphatic spread. Cancers that spread in the peritoneal cavity often share a common feature in that they tend to over-express glycoprotein molecules, which often is associated with more aggressive cancers. Gaining a better understanding of these molecules may provide an important target in the development of future treatments, an area that Dr. Foster is actively researching.  

Steve Shufelberger walks his dachshund almost daily.

The first goal of the surgical procedure is to remove all visible sites of the cancer. The removal of the cancer is the most challenging part of the procedure and often requires removal of several abdominal organs. “Even when all visible disease is removed, we know that microscopic cells in the peritoneal cavity that were the building blocks for the larger tumors that were removed, can lead to early recurrence of disease,” says Dr. Foster. “The hot chemo destroys these cells as well as small nodules that may not be amenable to removal.”

Hot chemo can complement traditional chemotherapy used for patients with metastatic cancer and offers several advantages. First, the hot solution can be delivered directly to the site of disease and bathes the entire peritoneal cavity at higher levels, which cannot be achieved with traditional intravenous (IV) chemotherapy. The chemotherapy doses are four to five times higher than what can be used in IV chemotherapy and does not cause toxicity to the abdominal surfaces. Additionally, research has shown that heat by itself kills cancer cells. Heat combined with chemotherapy amplifies chemo’s effectiveness and adds another mechanism to induce cancer cell death.

“Cancer cells do not dissipate heat well,” explains Dr. Foster. “So for this to work, we had to find a temperature warm enough to kill the cancer cells, but not too hot to damage the healthy tissue inside the body or impede healing after surgery.” That temperature is approximately 42 degrees Celsius or 108 degrees Fahrenheit.

Clinical studies have confirmed its effectiveness. Hot chemo treatment was first used for the treatment of appendix cancers, which historically were very difficult to treat due to the propensity of this disease to spread and to recur after surgical removal. The median survival for high-grade appendix tumors before hot chemo was introduced was typically less than a year. Hot chemo has extended survival from three to 10 years and for many patients provides a lifetime without relapse, says Dr. Foster. It is the only effective therapy for patients with appendix carcinomas as well as malignant peritoneal mesothelioma, which now boast five-year survivals over 50 percent compared to less than a year prior to the introduction of hot chemotherapy.

“This treatment has also shown improved outcomes for other common abdominal cancers with carcinomatosis (spreading in the peritoneal cavity) such as colorectal and ovarian cancers, increasing the five-year survival for these patients by 30 to 60 percent,” says Dr. Foster. “Even in patients with whom we don’t achieve a cure, we double the median survival time and improve quality of life.”

“One of the keys to success,” says Dr. Foster, “is getting to patients early in their diagnosis so we can have the opportunity to potentially eradicate all of their disease. Studies show that this treatment works best when minimal residual disease is achieved after cancer removal. This typically doubles and triples long-term survival for these patients.”

There is no age limit for hot chemo qualification. Dr. Foster says he has treated patients who range in age from 20 to 80 years old.

Recovery is typically the same as for any major abdominal surgery, says Dr. Foster. Depending on the type of cancer, hot chemo may or may not be followed by administration of IV chemotherapy. In diseases like colon and ovarian cancers, chemotherapy is often administered in conjunction with hot chemo before and/or after surgery. “By eradicating all of the disease, the risk of short-term relapse is reduced and the need for subsequent chemotherapy can be reduced,” says Dr. Foster.

Unfortunately, abdominal cancers can recur even with early treatment. Patients can be treated again with additional surgery and hot chemo. “Cancer really needs to be thought of as a chronic disease,” says Dr. Foster. “Once you have it, you have a lifetime risk of relapse. However, doing everything possible early to put the disease in remission is the best strategy to reduce the risk of recurrence.”

Dr. Foster is the only physician in the Midwest who performs the hot chemo procedure. While the procedure is more commonly used in Europe, it is not widely performed here, as new medical approaches take much longer to gain acceptance in the U.S. One of the barriers to acceptance is that since it is performed in conjunction with surgery, it may add up to two additional hours to what might already be a long surgical procedure. Additionally, there are misconceptions about in-hospital recovery times. Dr. Foster says, “The average length of stay is seven to 12 days, which is the same time required for pancreatic or hepatic cancer resections without hot chemo.”

But Dr. Foster’s caseload is increasing. He is currently performing one to two procedures a week. “Word is spreading,” he says. “Once people know about surgical options, and referring physicians see that it can be done safely with tangible benefits, acceptance will continue to grow.”

Shufelberger is now one of his strongest proponents. Shufelberger’s surgery in 2006 involved removal of all areas with disease involvement. This was followed by hot chemo treatment for 90 minutes. He recovered in the hospital for eight days. After six to eight weeks, Shufelberger was back to work putting in nine- to 10-hour days as a manager at a local Baker’s grocery store.

“One of the keys to success is getting to patients early in their diagnosis so we can have the opportunity to potentially eradicate all of their disease.”
Jason Foster, MD

“Everything went very well,” says Shufelberger. “I had no complications. I’m just glad that I could be treated as easily as I was. I watched my sister-in-law go through radiation therapy and long-term chemotherapy. It really took its toll on her.”

Since treatment, Shufelberger has clinically remained cancer-free. In April 2010, he underwent surgery to repair an umbilical hernia. During surgery, Dr. Foster also looked for any hidden lesions that might not be detected on CAT scans and found only a few traces of microscopic disease. He removed them and performed a second hot chemo treatment to destroy these. “The fact that after four years there were only a few rare sites of microscopic disease is testament to the efficacy of this treatment,” says Dr. Foster.

Neither time did Shufelberger experience sickness or nausea. The worst of his symptoms was several months of fatigue. “It’s never stopped me from doing anything I want to do,” says Shufelberger, who can be seen walking his dachshund around Zorinsky Lake four to five times a week.

Shufelberger, who moved to Omaha from Hutchinson, Kan., in 2003, says he feels very fortunate to have found Dr. Foster and UNMC. Shufelberger says he actually looks forward to seeing Dr. Foster every six months. “He’s a guy I’d want to meet outside of the medical arena,” he says. “He’s very personable. He doesn’t talk down to you and he never seems to be in a hurry. And when you’re going through what I did, that’s what you need.

“I would recommend him to anyone. Sometimes I wonder what might have happened if I hadn’t moved here and met Dr. Foster. It’s something I don’t like to think about. We’ll never know — thank goodness. If we ever had to move again, I’d keep coming back to see Dr. Foster. It doesn’t matter how far we’d have to travel.”

Next article in the Spring | Summer 2011 issue of One Thousand And One:
Charting a Familiar Course