Tumor microsatellite instability (MSI) affects colorectal cancer prognosis

High levels of microsatellite instability (MSI-H) in colorectal tumors led to better survival for patients with stage II and III colorectal cancer in an Italian study reported in the December 1, 2005 issue of [Clinical Cancer Research](http://clincancerres.aacrjournals.org/cgi/content/abstract/11/23/8332). In addition, fluorouracil-based chemotherapy did not improve survival for patients with MSI-H tumors.

Microsatellites are repeated sequences of DNA in a gene. In the normal cell, these sequences are of a fixed length and don’t change. However, changes or mutations in DNA can lead to cancer. Ordinarily *mismatch repair genes* respond to changes in DNA, repair it, and prevent the potentially malignant mutations. When the mismatch repair gene itself is faulty, these repairs are not made and cancer results. In some colorectal tumor cells, many errors in DNA accumulate. Strands of DNA (microsatellites) are either shorter or longer than usual. This condition is *microsatellite instability.*

Not all tumors exhibit high levels of microsatellite instability, although it is a feature of hereditary non-polyposis colon cancer (HNPCC) where inherited mutations in mismatch repair genes lead to early colon, uterine, and other cancers. In addition to patients with HNPCC, some sporadic or non-inherited tumors will show MSI-H.

In the current study, 1,263 tumors were tested for microsatellite instability and colorectal cancer survival was analyzed. 256 tumors were MSI-high (20.3%). They were more often on the right side of the colon, of an earlier stage, mucinous, and poorly differentiated.

Stage, grade of differentiation, location of tumor, patient age and gender, and MSI status were all significant factors in prognosis. MSI-H was particularly advantageous for stage II and III tumors where the use of fluorouracil chemotherapy seemed to make no difference in survival. In initial analysis, patients with hereditary MSI-H cancer (HNPCC) showed a survival advantage over those with sporadic MSI tumors, but that advantage disappeared when other factors such as age and stage at diagnosis were also included in the analysis.

Piero Benatti and colleagues concluded:

The type of genomic instability could influence the prognosis of CRC, in particular in stages II and III. Fluorouracil-based chemotherapy does not seem to improve survival among MSI-H patients. The survival benefit for patients with hereditary non–polyposis colorectal cancer is mainly determined by younger age and less advanced stage as compared with sporadic MSI-H counterpart.

Posted by Kate Murphy on December 6th, 2005
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Having supplemental insurance increases Medicare patients in clinical trials

In 2000, Medicare policy changed to cover routine medical costs for Medicare patients enrolled in clinical trials. The policy change increased the percentage of older adults in clinical trials but only for those Medicare recipients who also had supplemental insurance. Those with Medicare coverage only were no more likely to be part of a clinical trial.

In a [study reported in an early online edition of the *Journal of Clinical Oncology*](http://www.jco.org/cgi/content/abstract/JCO.2005.02.8928v1?etoc) analysts from the Southwest Oncology Group (SWOG) compared the percentages of patients 65 and over enrolled in SWOG clinical trials before and after the Medicare policy change.

Previously, from 1993-1996, 25% of patients in SWOG clinical trials were 65 or older, while 63% of people with cancer were at least 65 years of age. From 1997 through 2000, the year that Medicare policy changed, 31% of SWOG enrollees were at least 65. In the years 2001 through 2003, the percentage increased to 38%.

However, in analyzing payment patterns, the researchers found that the increase in enrollment was true only for those Medicare patients who also had supplemental insurance.

Joseph M. Unger and the SWOG team concluded:

Method of payment analyses provided evidence that the Year 2000 Medicare policy change had a positive impact, but only for those patients with supplemental private coverage of coinsurance costs. Improvements in the Medicare payment structure could further increase older patient participation in clinical trials.

Posted by Kate Murphy on December 6th, 2005
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Dangerous strain of C. Difficile causing outbreaks of diarrhea

A new strain of the bacteria *Clostridium difficile* is emerging in epidemic proportions in health care facilities in the United States and Canada. Two studies reported early online in the *New England Journal of Medicine* studied cases at [twelve hospitals in Quebec](http://content.nejm.org/cgi/content/abstract/NEJMoa051639) and [seven hospitals and an extended care facility in the United States.](http://content.nejm.org/cgi/content/abstract/NEJMoa051590).

Both the numbers and severity of Clostridium difficile-associated disease (CDAD) appear to be increasing in the United States according to researchers at the Centers for Disease Control, and they attribute this to the the new strain which they have labeled BI/NAP1. While the strain had been seen in rare cases previously by the CDC, it was a major contributor to CDAD in the nearly 200 cases studied in US health care facilities.

BI/NAP1 is resistant to fluoroquinolones. Some of the brand names for the fluoroquinolones are Cipro, Avelox, Floxin, Levaquin, Maxaquin, Noroxin, and Tequin. The researchers believe that increasing use of these drugs in health care facilities has allowed the stronger, drug-resistant bacterial strain to emerge and flourish.

The CDC studied samples from nearly 200 patients in 8 health care facilities. More than half the cases of CDAD included the BI/NAP1 strain. Symptom-causing toxins were significantly higher in those cases with 18 times the level of toxin A and 23 times the level of toxin B. The rare binary toxin CDT was also found in samples positive for the BI/NAP1 strain.

The CDC research team found that the strain was identical to one identified in Canada and [described by Vivian G. Loo, M.D. in the NEJM](http://content.nejm.org/cgi/content/abstract/NEJMoa051639). Dr. Loo and her team studied over 1,700 hospitalized patients with c.difficile disease over a six month period in 2004. They found over 80% of them had infections resistant to fluoroquinolones and positive for the binary toxin.

Overall nearly 7% of patients in the Canadian study died as a result of c. difficile, a substantially larger percentage than had been seen previously. Both the rates of infection and death rates increased with age. In addition, some patients in both Canada and the US required removal of their colon (*colectomy*).

Compared to the control cases, patients with CDAD were almost four times as likely to have been treated with fluoroquinolones or cephalosporins prior to developing the severe diarrhea.

L. Clifford McDonald, M.D. and the Centers for Disease Control say that prevention is key to controlling the outbreak. They suggest that:

+ Health care facilities track the incidence of *c.difficile associated disease* including outcomes for patients diagnosed with CDAD.
+ Procedures be developed to identify and treat CDAD early.
+ Patients be isolated and contact precautions (gowns and gloves) be used by health care workers.
+ Handwashing with soap and water be strictly observed. Since c.difficile bacteria is resistant to alcohol, alcohol-based hand sanitizers should not be used.
+ Most important is restrained use of the antibiotic agents such as the fluoroquinolones that are associated with the disease.

Additional discussion of the studies can be found on [MedPage Today](http://www.medpagetoday.com/InfectiousDisease/PublicHealth/tb/2254)

Posted by Kate Murphy on December 5th, 2005
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Talking about cancer concerns helps both patient and caregiver

Patients and caregivers both sometimes don’t tell each other about cancer-related concerns. However, a study of patients with gastrointestinal cancer and their spouses showed that disclosing concerns was not harmful to either patient or caregiver. Furthermore, low levels of disclosure and high levels of holiding back increased psychological distress for both. Couples who withheld problems had more difficulty with their relationship.

Laura S. Porter and a team at Duke University Medical Center [questioned 47 patients and their spouses](http://www3.interscience.wiley.com/cgi-bin/abstract/109924613/ABSTRACT) about how much they disclosed concerns about cancer and how often they “held back.” Patients also answered questions about their quality of life, and spouses responded to a measure of caregiver-strain. All participants completed measures of psychological distress and relationship functioning that included intimacy, empathy,and avoiding or criticizing each other.

Overall most of the couples reported moderately high levels of disclosure and low levels of holding back.

The study appears in the December 2005 issue of *Psycho-Oncology.*

Posted by Kate Murphy on December 2nd, 2005
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