Changing Clinical Practice -- Familial Colorectal Cancer Type X
Investigators: Noralane Lindor, M.D.; Kari Rabe; Gloria Petersen, Ph.D.; Mariza de Andrade, Ph.D.; Stephen Thibodeau, Ph.D.; Lisa Boardman, M.D.; and collaborators from a number of other institutions

The American Cancer Society reports that colorectal cancer is diagnosed in nearly 154,000 people each year in the United States. A highly-preventable cancer if found early, colorectal cancer is the focus of many researchers at Mayo Clinic Cancer Center, who are searching for better ways to screen for this disease, thus enabling earlier intervention/prevention.

One of the primary ways to improve screening is to better identify individuals at higher risk to develop colorectal cancer. Through collection and analysis of environmental and genetic information of large groups of people, risk estimates can be developed across populations.

Dr. Lindor and her colleagues took this type of research to the next level. Reported in The Journal of the American Medical Association in 2006, risks were refined for a sub-group of individuals who meet the Amsterdam-I criteria (AC-I) for hereditary nonpolyposis colorectal cancer (HPNCC), resulting in a higher risk of developing colorectal cancer than the general population. Families meeting AC-I criteria have heretofore been diagnosed with HPNCC-Lynch syndrome; however, pedigree-defined families comprise two entities.

It has long been known that about 60 percent of people that meet the AC-I have an inherited abnormality in a DNA mismatch repair gene. This entity may be called Lynch Syndrome. The cancer risks associated with the hereditary disorder are well defined and significantly greater than in the general population. Dr. Lindor and her inter-institutional team of investigators sought to determine if remaining families that fulfilled the AC-I criteria but did NOT have this genetic abnormality have the same risks as those with true Lynch Syndrome. After analysis of of 161 families that all fit the AC-I critieria, they reported that those without evidence of DNA mismatch repair gene defect had lower risks for colorectal cancer than did the Lynch Syndrome families. In addition, risks for non colonic cancers were not appreciably increased. Lastly, those with no DNA mismatch repair deficiency has older ages of diagnosis of colorectal cancer than did the Lynch Syndrome families (60.7 vs 48.7 years).

These findings negate the common practice of applying the HPNCC-Lynch syndrome diagnosis across the board for AC-I families. Instead, Dr. Lindor and colleagues recommended the use of a new term to describe the cancers of individual families without the abnormality -- Familial Colorectal Cancer Type X, reserving the HNPCC-Lynch Syndrome diagnosis for those families with the DNA mismatch repair deficiency.

More research needs to be done, but the research appears to indicate that this DNA abnormality is related not only to colorectal cancer, but also to uterine, stomach, urinary tract (including kidney), ovary and small intestine cancer. There is some evidence of increased risk for these families of pancreatic and liver cancer as well, whereas for the other AC-I families, only colorectal cancer risk is elevated beyond that of the general population.

Dr. Lindor is also the primary investigator of the Mayo site of the Colon Cancer Family Registry (CFR), which is a National Cancer Institute (NCI)-supported consortium of six centers initiated in 1997 to establish a comprehensive collaborative infrastructure to facilitate interdisciplinary studies of the genetics and epidemiology of colorectal cancer. The Colon CFR has been the basis for multiple studies.

Finding Better Options -- Liver Transplant Life Expectancy Increased Through Neoadjuvant Chemoradiation
Investigators: David Rea, M.D.; Julie Heimbach, M.D.; Charles Rosen, M.D.; Michael Haddock, M.D.; Steven Alberts, M.D.; Walter Kremers, Ph.D.; Gregory Gores, M.D.; and David Nagorney, M.D.

Mayo Clinic Cancer Center researchers study a variety of cancers, ranging from the most common to the rarest. They seek to lessen the burden on society -- not just for Americans, but for those who suffer from cancer worldwide. Bile duct cancer affects only a small number (4,600) people in the United States each year, reports the American Cancer Society, although the incidence is increasing. However, it disproportionately appears in Asia and the Middle East due to a common parasitic infection of the bile duct. It also is more commonly found in men than in women.

Conventional therapy for people diagnosed with hilar cholangiocarcinoma, cancer in a specific area of the bile duct system, is to surgically remove the tumor. This surgery often includes removing a large part of the liver. However, for patients with extensive hilar cholangiocarcinoma that invades too much of the liver to leave enough for survival, liver transplant has long been thought to be the only option that has a chance to succeed.

In the late 1980s and early 1990s, number of researchers around the world reported poor 5-year survival rates (20 to 30 percent) and over 50 percent recurrence using liver transplantation and surgical removal of the cancer. This caused some reluctance to move forward with liver transplants, but as it still provided hope for a small group, Mayo Clinic continued to offer the option.

Some Mayo patients who did not receive surgery were treated with primary radiotherapy and chemosensitization, resulting in 22 percent reaching 5-year survival rates. Because of the promising results seen in this area, it was logical to attempt to combine the two marginally-successful strategies to see if increases in survival rate could be achieved for a larger percentage of patients. Transplant specialists, radiation oncologists, medical oncologists and gastroenterologists worked together to design a treatment protocol that combined radiotherapy, chemosensitization and liver transplantation for appropriate patients.

In 2004, Mayo Clinic researchers were able to report possibly the largest ever increase in survival rate through a change in practice, showing 82 percent reaching 5-year survival, of the initial 28 patients to receive the protocol from 1993 through 2004. Their findings were published in the September 2005 issue of Annals of Surgery.