Cervical dysplasia

Cervical dysplasia: Changes from normal in the cells lining the cervix of the uterus. Cervical dysplasia involves a sequence of cellular changes from mild to severe that are not yet cancerous but constitute the prelude to cervical cancer.

The diagnosis of cervical dysplasia is made from the PAP smear. As a rule, cervical dysplasia is found in no more than 5% of PAP smears. The incidence peaks in women 25 to 35 years of age. Risk factors include multiple sexual partners, the early onset of sexual activity (before age 18), early childbearing (before age 16) and a history of an STD (a sexually transmitted disease such as chlamydia, genital warts gonorrhea, genital herpes, and HIV). In a woman with HIV, the speed of changes in cervical dysplasia is accelerated.

The treatment depends on the degree of dysplasia. It may include cryotherapy (freezing the area) and conization (removal of a cone of tissue from the cervix). The aim is to prevent full-fledged cervical cancer.

Familial adenomatous polyposis

nFamilial adenomatous polyposis: Abbreviated FAP. A syndrome characterized by the formation of thousands of polyps in the colon and rectum with colorectal cancer the inevitable consequence. Polyps can also occur in the stomach, duodenum and the terminal ileum.

The polyps most often begin to form at puberty. And colon cancer usually occurs 10 to 15 years thereafter. The average age of diagnosis of familial polyposis is 25 years of age, with cancers developing at age 20 to 30. However, cancers may arise anywhere from late childhood to the sixties.

The syndrome is an autosomal dominant disorder with high penetrance and highly variable expressivity. A person with the disease thus has a 50% chance of passing the gene on to each of their children. Most people who receive the gene almost always manifest the disease although the expression of the disease can vary markedly from person to person.

The gene that is mutated in this disorder, symbolized APC for adenomatous polyposis coli, has been characterized and its protein identified. A variety of mutations in the APC gene have also been identified. The APC gene maps to chromosome 5 in region 5q21-q22.

Gardner syndrome (with polyps of the colon, extra bowel tumors, especially osteomas, and a rather characteristic abnormality of the retina of the eye) is now known not to be a wholly different disease but rather to be a variant of FAP, caused by a mutation in the APC gene.

Familial adenomatous polyposis (FAP) has also been called multiple polyposis of the colon, hereditary polyposis coli, familial multiple polyposis, familial polyposis of the colon (FPC) and adenomatous polyposis coli. The designation familial adenomatous polyposis (FAP) is most often used today, based in part on the appreciation that the polyps are not confined to the colon.

One Alcoholic Drink Per Day Increases Women's Cancer Risk

Don't women don't have enough to worry about? The economy is a mess. Global warming might leave their children with a wrecked planet. So, what now? Well, that little guilty pleasure -- a glass of wine at the end of the day -- might not to be such a good idea after all.

A new study involving nearly 1.3 million middle-aged British women -- the largest ever to examine whether alcohol increases a woman's risk of cancer -- found that just one glass of chardonnay, a single beer or any other type of alcoholic drink per day poses a danger.

"That's the take-home message," said Naomi E. Allen of the University of Oxford, who led the study being published March 4 in the Journal of the National Cancer Institute. "If you are regularly drinking even one drink per day, that's increasing your risk for cancer."

Understandably, the study might leave many women scratching their heads -- and perhaps needing a drink more than ever -- given all the talk about red wine being something akin to a fountain of youth.

"I thought drinking wine was good for you," said Mirella Romansini, 27, of Chevy Chase, outside Paul's liquor store in Northwest Washington. "Now they are saying it increases your risk for cancer? Yes, I would say I'm surprised."

Romansini is hardly alone. At least half of U.S. women drink sometimes, and even the Dietary Guidelines for Americans, the government's official bible on what we should be putting into our mouths, say alcohol can have "beneficial" effects, allowing women up to one drink a day (men get two, of course).

Confused? It turns out the guidelines were never intended to recommend that anyone drink for their health. Yes, it's true that studies have indicated that moderate drinking might cut the risk of heart disease and other ailments. And researchers have identified a substance in red wine (remember resveratrol?) that could offer a host of benefits.

But officials have long worried about sending the wrong message, giving people who should never drink -- young people, pregnant women, those prone to alcoholism -- permission to abuse alcohol. As a result, they have long tried to walk a fine line between acknowledging the possible benefits of alcohol without encouraging people to start drinking or to abuse it. The guidelines were intended to set an upper limit on what might be safe, not a recommended daily dose.

"It's a level of consumption that is generally has been found in scientific studies to be associated with a relatively low risk of harms," said Robert D. Brewer of the federal Centers for Disease Control and Prevention. "But low risk does not mean no risk."

In fact, many previous studies have found that alcohol appears to increase the risk of breast cancer, and that heavy drinking could make men and women prone to other cancers as well. The new study is a large-scale attempt to explore all cancer risks posed by more typical drinking levels and a spectrum of alcoholic beverages.

Allen and her colleagues analyzed data collected by the Million Women Study, which has been gathering detailed information from 1.28 million women ages 50 to 64 since 1996. The researchers examined how much alcohol they reported consuming when they volunteered for the study and again three years later, and examined whether there was any link with the 68,775 cancers they developed over an average of next seven years.

Even among women who consumed as little as 10 grams of alcohol a day on average -- the equivalent of about one drink -- the risk for cancer of the breast, liver and rectum was elevated, the researchers found. Among women who also smoked, the risk of mouth and throat cancer also increased.

Based on the findings, the researchers estimated that about 5 percent of all cancers diagnosed in women each year in the United States is due to low to moderate alcohol consumption. Most are breast cancers, with drinking accounting for 11 percent of cases -- about 20,000 extra cases each year -- the researchers estimated.

In any group of 1,000 U.S. women up to age 75 who consumed an average of one drink a day, the researchers calculated there would be 15 extra cancers; two drinks per day would result in 30 extra cancers and so forth.

The risk appeared the same regardless of whether women drank wine, beer or any other type of alcohol. Allen noted that even less than one drink per day might increase the risk.

"There doesn't seem to be a threshold at which alcohol consumption is safe," she said.

Several researchers noted that the findings were essentially consistent with previous studies, and despite its size the study does have shortcomings. The researchers could not, for example, distinguish between women who drank only one or two drinks every day and those who drank seven drinks all at once. Some researchers worried the findings would unnecessarily frighten women and deprive them of the possible health benefits of an occasional drink.

"We can't use this to scare people away from alcohol," said Eric Rimm of the Harvard School of Public Health.

Allen plans to do another analysis of data from the study to try to determine whether the net risks from cancer outweigh any heart benefits. But others were doubtful.

"Among women, the major cause of death by far during the middle age years is cancer," Michael S. Lauer and Paul Sorlie of the National Heart, Lung and Blood Institute noted in a editorial accompanying the study. "For this large group, the only reasonable recommendation we can make is there is no clear evidence that alcohol has medical benefits."

As it turns out, the federal government is rewriting its dietary guidelines, including the part about alcohol consumption, and will consider the new study in that process.

"No one study is ever sufficient to make a recommendation," said Linda Van Horn, a professor of preventive medicine at Northwestern University who is chairing the committee revising the guidelines. "But it will be added to the body of literature that will be reviewed."

In the meantime, several experts said women should consult with their doctors about whether they should drink.

"It really comes down to a personal decision based on their own history and risk factors," Rimm said. "But it shouldn't be based only on health. Some people drink for cultural reasons, some people drink for religious reasons. I personally think it enhances the flavor of meals, and some people think the company you're with."

Smoking and Obesity

Many people know the risks of smoking, and many people know the risks of being over-weight, but not many studies have looked at the mortality risk of the two factors together. As expected, there was an elevated mortality risk that was higher than the risk of any of the two factors by themselves. The research paper’s design was very good in standards of following the requirements of the information needed in a retrospective cohort. The sample size that was used was large >80,000. Of those, over 64,000 were women. Researchers made sure to remove any people that had a history of prior cancer or myocardial infarction (MI). They used a questionnaire to ascertain the exposed and non-exposed groups. Some of the factors looked at in the questionnaire was height, weight, alcohol use, and smoking habits, among other things.

Body mass index (BMI) and smoking status were both stratified to see how the two factors affect mortality risk. The causality of the two factors were very clear in the results that where concluded. It was found that there was a 3.5 to 5 fold increase in all-cause mortality of smokers that were very obese (BMI > 35). In contrast if you where just very obese and did not smoke your Relative Risk (RR) for all-cause mortality was lower (1.4—2.5). The strongest cause and effects found in this study was that of smoking and very obese women who had a 6-11 fold increase in circulatory disease mortality.

In looking at the data I did not see any mistakes in the correlations that were drawn. The confidence intervals used in the study ranged from .005-.0001 so they are definitely in the realm of scientific creditability. Some of the areas that could prove a problem is the fact that the people in the study filled out the questionnaire themselves, and people could have been dishonest about weight or height, which could have made the calculation on BMI skewed to the left, meaning a lower BMI than what they actually are. I think this because most people say they weigh less then they do. Also, there is a problem with the former smokers if they started to smoke again after the survey. Their mortality information should have been with the smokers instead of the non/former smokers.

In all, I think the information obtained from this study is an important find for policy makers, in where money should go in preventative health care, and to which of the sexes should it be focused on more (female). By using this information correctly policy makers can maximize the amount of lives saved.

works cited--
D. Michal Freedman. (2006). The Mortality Risk of Smoking and Obesity Combined. American Journal of Preventive Medicine, 31(5) 355-362

Nanoparticle 'Smart Bomb' Targets Drug Delivery to Cancer Cells

Researchers at North Carolina State University have successfully modified a common plant virus to deliver drugs only to specific cells inside the human body, without affecting surrounding tissue.

These tiny "smart bombs" - each one thousands of times smaller than the width of a human hair - could lead to more effective chemotherapy treatments with greatly reduced, or even eliminated, side effects.

Drs. Stefan Franzen, professor of chemistry, and Steven Lommel, professor of plant pathology and genetics, collaborated on the project, utilizing the special properties of a fairly common and non-toxic plant virus as a means to convey drugs to the target cells.

The researchers say that the virus is appealing in both its ability to survive outside of a plant host and its built-in "cargo space" of 17 nanometers, which can be used to carry chemotherapy drugs directly to tumor cells. The researchers deploy the virus by attaching small proteins, called signal peptides, to its exterior that cause the virus to "seek out" particular cells, such as cancer cells. Those same signal peptides serve as "passwords" that allow the virus to enter the cancer cell, where it releases its cargo.

"We had tried a number of different nanoparticles as cell-targeting vectors," Franzen says. "The plant virus is superior in terms of stability, ease of manufacture, ability to target cells and ability to carry therapeutic cargo."

Calcium is the key to keeping the virus' cargo enclosed. When the virus is in the bloodstream, calcium is also abundant. Inside individual cells, however, calcium levels are much lower, which allows the virus to open, delivering the cancer drugs only to the targeted cells.

"Another factor that makes the virus unique is the toughness of its shell," Lommel says. "When the virus is in a closed state, nothing will leak out of the interior, and when it does open, it opens slowly, which means that the virus has time to enter the cell nucleus before deploying its cargo, which increases the drug's efficacy."

The researchers believe that their method will alleviate the side effects of common chemotherapy treatments, while maximizing the effectiveness of the treatment.

Zoledronic Acid May Help Reduce Breast Cancer Growth

For premenopausal women with early hormone-responsive breast cancer, bisphosphonates during adjuvant endocrine treatment may improve disease-free survival, researchers found.
Action Points

* Explain to interested patients that zoledronic acid is given to breast cancer patients on endocrine therapy to protect bone health.

Note that zoledronic acid has been shown to have potential antitumor activity in preclinical and early phase studies.

The addition of zoledronic acid (Zometa) reduced the risk of disease progression by 36% compared with adjuvant endocrine therapy alone (absolute difference -3.2 percentage points, P=0.01), found Michael Gnant, M.D., of the Medical University of Vienna, and colleagues.

While the randomized trial showed no mortality benefit, toxicity was minimal, they reported in the Feb. 12 issue of the New England Journal of Medicine.

The results confirm the initial report of the data at last year's American Society of Clinical Oncology meeting.

This effect was comparable to the absolute advantage in disease-free survival seen in prior trials for aromatase inhibitors versus tamoxifen among postmenopausal women with early breast cancer, the researchers noted.

Given the similar advantage of aromatase inhibitors in one prior study of premenopausal women, their Austrian Breast and Colorectal Cancer Study Group trial was also designed to compare endocrine treatments.

The study included 1,803 premenopausal women with endocrine-responsive stage I or II breast cancer who were given the gonadotropin-releasing hormone analog goserelin (Zoladex, 3.6 mg subcutaneously every 28 days) after primary surgery.

They were randomized to adjuvant treatment with tamoxifen (20 mg per day given orally) or anastrozole (Arimidex) at 1 mg per day given orally) with or without zoledronic acid (4 mg given intravenously every six months) for three years.

However, unexpectedly, anastrozole did not improve outcomes among premenopausal women in the study at a median follow-up of 47.8 months. The findings compared with tamoxifen included:

* No effect on disease-free survival (hazard ratio 1.10, P=0.59)
* No impact on recurrence-free survival (HR 1.11, P=0.53)
* No advantage for overall mortality (HR 1.80, P=0.70)

The difference compared with postmenopausal women might have been "because of the dominant effect of ovarian suppression on estrogen levels in premenopausal women," the researchers suggested. "Moreover, long-term administration of goserelin can reduce androgen levels, thereby limiting the available substrate for aromatase activity."

Other findings for the addition of zoledronic acid compared with endocrine therapy alone included:

* Improved disease-free survival rates (94.0% versus 90.8%, P=0.01)
* A 36% relative reduction in risk of disease progression (P=0.01)
* Improved recurrence-free survival at 47.8 months (94.0% versus 90.9%, P=0.01)
* A 35% reduction in risk of recurrence (P=0.02)
* No difference in risk of death (HR 0.60, P=0.11).
* No significant effect on survival free of bone metastasis despite a 32% risk reduction (HR 0.68, P=0.22), which the researchers attributed to a small number of events

The number needed to treat with zoledronic acid to prevent disease progression in one patient was 31 in the study, "consistent with the number needed to treat for cancer therapies that in the past have caused a shift in treatment standards," such as docetaxel (Taxotere) and paclitaxel (Taxol), Dr. Gnant's group noted.

The researchers noted no excess toxicity aside from "known drug-safety profiles." Zoledronic acid-treated patients had slightly higher incidences of bone pain (35% versus 25%), arthralgia (24% versus 18%), and fever (9% versus 2%), with apparently additive effects for the bone-related adverse events.

Three suspected cases of osteonecrosis of the jaw among zoledronic acid-treated patients were all ruled out after review of dental records. There were also no signs of renal toxicity.

The effect on breast cancer may be explained by preclinical and early phase studies that showed zoledronic acid inhibited tumor-cell adhesion, invasion, and proliferation and induced tumor cell apoptosis, acted synergistically with chemotherapy agents, and exerted antiangiogenic effects, Dr. Gnant's group said.

How to get money for not smoking

When trying to quit smoking, it can help to keep your eyes on the prize — especially if that prize is $750.

A new study shows that smokers who earn financial incentives are three times more likely than others to kick the habit. In an experiment with nearly 900 smokers employed by General Electric, 15% of those given incentives were smoke-free after a year, compared with 5% of those who weren't eligible for cash rewards.

The study rewarded employees for incremental milestones — $100 for completing a smoking-cessation class, another $250 for being smoke-free after six months and $400 more for being smoke-free after a year.

"People are drawn to tangible things," says author Kevin Volpp, a doctor at the Philadelphia VA Medical Center and director of the Center for Health Incentives at the University of Pennsylvania. "It makes it easier for you to do in the short term what you know is in your long-term best interest."

The incentives paid for themselves in about three years, says co-author Robert Galvin, GE's chief medical officer. GE plans to offer a version of the smoking-cessation program next year, although officials haven't yet decided the amount of the incentives.

Tobacco taxes also provide strong incentives to quit, says the American Cancer Society's Tom Glynn, who wasn't involved in the study. Research shows that each 10% increase in the cost of cigarettes reduces the teen smoking rate by 7% and the adult rate by 4%.

He says he understands that some people may question the wisdom of paying people to do something that's in their own best interest. But he notes that we already pay for health problems caused by smoking and obesity, through private insurance premiums and taxes for Medicare.

In the study in today's New England Journal of Medicine, researchers gave everyone information about local smoking-cessation classes and the company's coverage of drugs designed to help them quit. Half were also offered incentives. Each group had about the same number of heavily addicted smokers.

Quitters need all the help they can get, Volpp says, noting that 70% of smokers want to quit but only 3% succeed each year. And the relatively low quit rates in his study — in spite of incentives — underscore how difficult it is to quit, even with help.

Glynn hopes the study will inspire other businesses to help employees quit. "In the long run," he says, "stopping smoking pays off for everyone."

For help with quitting, call 800-QUIT-NOW

Circulating Tumor Cells Could Predict Prostate Cancer Outcome

Checking for changes in the number of circulating tumor cells (CTCs) could help doctors predict advanced prostate cancer patients' survival and response to treatment, U.S. researchers report.

They studied the association between CTC numbers (before and after treatment) and survival, along with other factors such as changes in levels of prostate-specific antigen (PSA) and baseline lactate dehydrogenase (LDH) in 164 prostate cancer patients starting first-line chemotherapy regimens.

High values of CTC numbers and PSA levels before treatment were associated with increased risk of death. At four, eight and 12 weeks after treatment, changes in CTC numbers were strongly associated with increased risk of death, while changes in PSA were only marginally associated with increased risk of death.

The findings confirm that pre-treatment CTC numbers help predict survival of prostate cancer patients starting first-line chemotherapy. CTC numbers also help monitor disease status and response to treatment, and CTC is a better predictor than PSA, the researchers said.

"CTC number[s] ... can be used to monitor disease status and might be useful as an intermediate endpoint of survival in clinical trials," wrote study author Howard Sher, of Memorial Sloan-Kettering Cancer Center in New York City. "Use as an intermediate or surrogate endpoint for survival could shorten the time line for drug approval," although "several prospective trials are needed to generate evidence to guide the use of biomarkers."

The study was published online and will appear in the March print issue of The Lancet Oncology.

More information

The American Cancer Society has more about prostate cancer.