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A century-old technique prevents extra tumor surgeries at Mayo

Dr. Gary Keeney talks about the use of frozen slides to diagnose cancer on Thursday, May 15, 2014 at the Mayo Clinic in Rochester.

Patients getting a lumpectomy for breast cancer at Mayo Clinic in Rochester are far less likely to need follow-up surgery than patients having the same procedure done at other clinics.

In fact, the rate of second surgeries needed after lumpectomies at other clinics is four times that at Mayo. The reason is Mayo's "frozen-section technique" — perfected at the request of the Mayo brothers themselves — which has been used for more than 100 years.

"We have something here that's going to minimize your risk of a second operation," said Dr. Judy Boughey, chair of the Division of Surgery Research at Mayo in Rochester .

The frozen section procedure involves sending removed tumor samples (including surrounding tissues) from the operating room directly to the nearby pathology lab. There, pathologists quick-freeze and shave off parchment-thin wafers of tissue samples, dye them and place them on slides for immediate analysis.

Most medical centers nationwide use some form of frozen sections. But it's rare to do the analysis and get the results while the patient is still in surgery. At other medical centers, slide review can take as long as 24 hours.


"This is something that we offer that other places don't offer — and this is what I would want for my relative," Boughey said.

Pathologists analyze the samples to be certain each has a "clean margin," meaning, essentially, that the surgeon successfully removed enough cancer-free tissue so that both the tumor and nearby cancerous cells have been taken out.

"Every patient specimen gets processed this way," Boughey said.

Labor-intensive job

It's a labor-intensive endeavor. The medical center in Rochester, even among Mayo facilities, is the only one with resources available for the task.

At other medical centers nationally, 13.2 percent of patients need a second lumpectomy when pathology tests indicate the surgical margins are not clean. At Mayo in Rochester, the need for a second surgery is just 3.6 percent because extra tissue can be removed immediately.

According to Mayo, the technique not only decreases the need for further surgery. It also decreases missed diagnoses, patient worry, travel time, and costs for the patient, insurance companies and hospital.

Even so, the standard throughout the country is not to do tissue analysis during surgery," Boughey said.


In large part, that can be attributed to staffing. It's a major undertaking, and big upfront cost, to institute Mayo's protocol for frozen-section analysis during patient surgeries, she said.

Pathologists and staff at Mayo in Rochester, for example, remain on duty "until the last surgeon shuts off the lights for the evening," Boughey said. They also remain on call overnight.

In Mayo operations, surgeons close up when "they feel we're cancer free" with lumpectomies, Boughey said. Other tumors in addition to breast cancer are reviewed in the same manner.

Altogether, patients remain under anesthesia for 10 to 20 minutes longer than they would otherwise. Boughey said during that time, "there's always something I'm working on towards their care."

While you were asleep

While the patient is under anesthesia after a tumor removal, a lot is happening in the pathology lab, said Dr. Gary Keeney, Mayo chair of anatomic pathology .

After the tissue sample is frozen, a precise cutting tool called a microtome "comes across and cuts around a 6-micron section," Keeney said. The thin piece of tissue is placed by a pathology technologist in a rinse, then stained and picked up with a glass rod to be placed on a labeled glass slide.

Pathologists scrutinize the results. A slide containing a sample with an unusual presentation can be projected on to a large overhead screen to allow a rapid team consultation. If needed, highly specialized experts from across the Mayo campus can connect remotely to weigh in on a difficult diagnosis.


Within minutes, the operating room learns the results.

Things move so quickly in the pathology lab at Mayo that "you wash your hands, sit down and it's done. It literally takes about 60 seconds," Keeney said.

"From a pathologist's perspective, you're really put in a spot. You make a diagnosis and the surgeon's going to take action on it," he said. If the pathologist says one thing, a patient's leg might get amputated. Whereas, if he says another, the patient's surgical team will close the surgical wound.

There are about 50 pathologists at Mayo in Rochester now who do rounds with cases at the start of each day. By about 7:30 a.m., surgeries begin and specimens start arriving in the pathology laboratory. Pathology assistants, with a four-year college degree and one to two years of pathology training, work with residents and fellows.

If cancer cells are found in a margin of the tissue, it's essential the surgeon knows at which point on the sample the cells were found, Keeney said.

"If there's a question about a specimen, we will often go down to the OR and talk to them about it," he said, because the surgeon knows the exact orientation the tumor had within the patient.

"We look at each other straight in the eye," Boughey said. "I know exactly where that is in the patient, because I just cut it out. ... It's the patient you and the pathologist are looking at at the same time."

Technique invented by Johns Hopkins

Johns Hopkins performed the first frozen section of breast tissue in 1872, so the technique was not invented at Mayo Clinic. But it was perfected there.

Doctors Will and Charlie Mayo had a keen interest in improving their surgical techniques.

"The brothers wanted a way to tell what was going on while a patient was still on the table," Keeney said. "So they recruited Dr. Louis B. Wilson ."

He was hired in January, 1905, and within a few months submitted his description for publication in the Journal of the American Medical Association.

At the end of the 19th century, "as surgeons tackled complex surgical procedures, they wanted to determine if a growth found at surgery was benign, malignant, infectious, or otherwise," says a 2005 retrospective in the Archives of Pathology and Laboratory Medicine about the centennial anniversary of the frozen-section technique at Mayo . "If a malignant growth was found, it was typically inoperable and the patient died soon afterward. Therefore, surgeons sought to investigate whether the microscopic examination of fresh tissue, namely the frozen section, could be used for intraoperative diagnosis and thus influence the surgical procedure."

The Mayo brothers had developed a reputation for impressive surgical outcomes.

To further improve it, Dr. Will Mayo wanted pathologists to find a way to find out whether a growth is cancer while the patient is still on the table.

Wilson "experimented with different techniques to cut tissue and found that by mounting the specimen between layers of elder pith, he could cut it by hand with a razor," says the Archives of Pathology and Laboratory Medicine piece.

"For freezing the tissues, he simply used the cold (-29 Celsius) January air; he placed the specimen outside the window for just a few minutes to freeze. The cuttings were then dipped into the methylene blue stain, washed with a salt solution, and mounted on glass slides using a glucose mixture."

Whether that's an exact depiction of how Wilson actually developed his technique remains uncertain — contemporaries question the veracity of oral histories that suggest he left samples on the windowsill.

However, what is known is that Wilson's technique remains in use at Mayo Clinic-Rochester today, very similar, with minor revisions, to the way Wilson performed it himself.

Recording technician James Warford prepares a slide with a fresh tumor sample on Thursday, May 15, 2014 at the Mayo Clinic in Rochester.

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