Thursday, November 26, 2009

Happy Thanksgiving

Today, America is celebrating Thanksgiving, my favorite holiday. Thanksgiving is not a religious holiday, but it is a deeply spiritual holiday. It's a time when we give thanks for this marvelous and mysterious universe. Most of us, on Thanksgiving, seek the company of family and friends. I hope that everyone, even those people who are unable to be with their loved ones, can enjoy this special time.

Happy Thanksgiving!

Jules Berman

Tuesday, November 24, 2009

Cancer prevention better than cancer screening

In the past several days, I've been blogging on the new guidelines issued last week for breast cancer screening (mammograms) and for cervical precancer screening (Pap smears). Basically, in both new sets of guidelines, the task forces raised the age at which routine screenings are started, because they felt that screening in the younger age groups found very few positive (malignant) cases. They reasoned that the small benefits of screening in the younger age groups are outweighed by the adverse affects of screening (false positives, unnecessary diagnostic tests and emotional trauma).

The public response was angry, countering that saving lives, even a small number of lives, is preferable to putting up with the non-life-threatening adverse effects of screening.

I'm sympathetic to both sides of the argument. Maybe there's another viewpoint that might put the debate into perspective.

While cancer screening tests have some value, the most effective way of reducing the cancer death rate is by cancer prevention. There are several drugs that can reduce the incidence of common cancers. Finasteride, for example, has been shown to reduce the incidence of prostate cancer by 30%. Though early studies indicated that finasteride mildly increased the incidence of highly aggressive prostate cancers, subsequent studies have shown that this is simply not the case. About 30,000 men die each year, in the U.S. from prostate cancer. Widespread finasteride use could lower the number of deaths by nearly 10,000 each year.

Finasteride is a drug that is used to reduce BPH (benign prostatic hyperplasia), and to reduce hair loss (under the name Propecia). It has a long history of use, and doctors understand the side-effects of Finasteride. The Merck patent on the use of Finasteride for the treatment of BPH has already expired, and the drug can be obtained as an inexpensive generic.

Ask yourself: "How many men do you know who take Finasteride to prevent prostate cancer?" I'm sure it's a very small number. Yet most women, over the age of 40, have mammographic examinations to detect breast cancer, and are prepared to fight anyone who tries to stop them.

There are a variety of agents that reduce the incidence of cancer. Most people are barely aware that the world-wide cancer death rate can be cut much more effectively with inexpensive anti-cancer agents than with expensive cancer screening tests. Both approaches are very important, but there seems to be a sociological blind-spot for prevention. I discuss this issue at some length in my recently published book, Precancer: The Beginning and the End of Cancer.

- © 2009 Jules Berman, Ph.D., M.D.

key words: cervical cancer, cin, dysplasia, precancer, precancerous lesions, hpv, Pap smear, Pap screening, cervical screening, cervical cancer screening, mammogram, mammographic screening, screening test, new recommendations, new guidelines, early cancer screening, cancer death rate, task force recommendations, ACOG, precancers, early detection, anticancer, anti-cancer, simvastatin, aspirin, calcium supplements

Friday, November 20, 2009

New guidelines for cervical (Pap Smear) screening

This seems to be the week for announcing new non-intuitive medical guidelines. My last three blogs focused on the November 16 mammography guidelines that recommended halting routine screening mammograms for women under 50.

Today (November 20, 2009), the American Congress of Obstetricians and Gynecologists (ACOG) announced their new guidelines for cervical (Pap Smear) screening. The major change is that the first Pap smear screening is now delayed until women are 21 years old. The prior recommendation was for women to get their first screening three years after they became sexually active, or age 21, whichever came first.

ACOG's official release statement , dated today, can be read at their web site. It's a short, one-page explanation, but it contains highly misleading statements.

Here's one: "Cervical cancer rates have fallen more than 50% in the past 30 years in the US due to the widespread use of the Pap test. The incidence of cervical cancer fell from 14.8 per 100,000 women in 1975 to 6.5 per 100,000 women in 2006."

Virtually every study of Pap smear screening shows a drop of at least 70% in the cervical cancer death rate, in populations that institute screening. I have no idea where they got the 50% number. The more disturbing part of their statement is the comparison of the U.S. cervical cancer death rate in 1975 with the death rate in 2006. This makes no sense.

If you want to measure the drop in the cervical cancer death rate before and after a screening tool has been implemented, you need to go back to a date preceding the introduction of the screening tool. In 1941, Papanicolaou and his coworkers published their paper establishing the diagnostic value of examining cervical smears to screen for cervical precancer. It took a while to implement the test nationwide, but it was certainly in common use in the 1960s. By the time 1975 came around, the Pap smear had already influenced the cervical cancer death rate. You should not be looking at the interim between 1975 and 2006 to measure the drop in cancer.

You've got to compare a pre-Pap date and a post-Pap date. The National Cancer Institute has done this for us. Cancer death rates for selected sites is shown for 1950 and 2005 in Table I-3. SUMMARY OF CHANGES IN CANCER MORTALITY, 1950-2005 AND 5-YEAR RELATIVE SURVIVAL RATES, 1950-2004 Males and Females, By Primary Cancer Site.

The table indicates that the cervical cancer death rate dropped 81.4% in white women. Furthermore, the uterine cancer death rate dropped 68.8% in the same 55-year period. Pap smears also screen for dysplasias and cancer of the endometrium (uterine lining), though with less sensitivity than for cervical screening.

That was not the only problem with the ACOG announcement. Another quotation is, "Although the rate of HPV infection is high among sexually active adolescents, invasive cervical cancer is very rare in women under age 21."

This statement gives the impression that the Pap smear is a screen for cervical cancer. It is not. The Pap smear is a screen for cervical precancer (referred to as dysplasias and CIN in the ACOG statement), not for cervical cancer, and the persons responsible for the ACOG statement don't seem to understand this. Precancers are the lesions that precede the development of cancer , and it may take precancers a decade or more to develop into cancers. Though the Pap smear can detect cervical cancers, the whole idea behind the test is to find precancers before they become cancers, when they can be treated by a simple excisional biopsy. The fact that cancers rarely occur in women under the age of 21 means that the neoplastic lesions most likely to be found by Pap smear in women under 21 are cervical precancers (i.e., the lesions that we're trying to find)!

The ACOG release also states: "Screening for cervical cancer in adolescents only serves to increase their anxiety and has led to overuse of follow-up procedures for something that usually resolves on its own."

Pap smear screening in adolescents actually has a number of useful purposes. It draws young women into the gynecologist's office, where a broad range of gynecologic diseases, in addition to cervical precancer, can be detected and treated. In fact, many infections of the vagina and cervix can be diagnosed by Pap smear. Their assertion that the Pap smear leads to over-use of follow-up procedures is also questionable. If there is an overuse of procedures following Pap smears (and I wouldn't know whether there is or isn't), then the ACOG should produce guidelines on the proper use of follow-up procedures. Reducing Pap smear screening in the under 21 age group because doctors do the wrong follow-up after they receive the smear report, seems absurd to me.

In summary, I don't really know whether the ACOG recommendations are any good. All I know is that some of the reasons that they provide in their release statement don't make much sense.

- © 2009 Jules J. Berman, Ph.D., M.D.

key words: cervical cancer, cin, dysplasia, precancer, precancerous lesions, hpv, Pap smear, Pap screening, cervical screening, cervical cancer screening, adolescents, teen-agers, screening test, new recommendations, new guidelines, early cancer screening, cancer death rate, task force recommendations, ACOG, precancers, early detection

About my book, Precancer: The Beginning and the End of Cancer. Nearly every type of cancer passes through a precancer phase, during which it cannot metastasize or invade other tissues. While medicine is not always successful in treating or curing advanced stages of cancers, recent advances in our understanding of carcinogenesis have helped us to develop strategies to prevent, diagnose, and treat many cancers at the precancer stage. Research in this field is escalating rapidly as the evidence increasingly shows that the number of annual cancer deaths could be drastically reduced through the effective treatment and cure of precancer lesions. This book begins by explaining why it has been so difficult to cure cancers, followed by a review of precancer biology, with descriptions of the most common precancer lesions. The final chapters provide practical socio-political and medical goals for precancer treatment, including discussions of the economics and politics of treating precancers.



I urge you to read more about this important topic. Google Books has provided a generous preview of this book.

More on new mammographic screening recommendations

I've had a chance to look at the evidence report issued by the United States Preventive Services Task Force that released the new recommendations for mammography screening earlier this week.

The evidence report is a public document available at:

http://www.ahrq.gov/clinic/uspstf09/breastcancer/brcanes.pdf

The report is entitled, Screening for Breast Cancer: Systematic Evidence Review Update for the U. S. Preventive Services Task Force, and was published this month by the AHRQ (the U.S. Agency for Healthcare Research and Quality). Anyone taking issue with the new recommendations should probably read the report before voicing their opinions.

For me, the biggest flaw in the report was the following line, where the task force wrote the limitations of the study:

"Limitations: Studies of older women, digital mammography, and magnetic resonance imaging are lacking."

I've been told that the latest digital mammograms produces superb images, that have diagnostic advantage over the images produced by the older instruments. If this is the case, then the labs that are currently using digital mammography may be doing a better job than the labs that are using the older equipment. More relevant to the task force report, the conclusion based on reviewing data using the old testing equipment may not be applicable for labs using the new equipment.

The problem with task force reviews, is that they're always working with data that lags behind the latest advances in the field. Basically, today's reality may be different from the reality that they reviewed.

It always seems to come back to two issues that I discussed in my blogs this week.

First, are all labs equal? Are there some labs that perform mammographic testing so well that a data review of their patients would show that mammographic screening in the 40-49 age group is justified, FOR THEM.

Second, as a screening test becomes more sensitive, and we start picking up small, early lesions and lesions of no biological consequence, how do we choose a clinically beneficial way of handling the test results?

The answer to the first question may involve using certified reference labs that perform tests at a high technical standard. If you want mammographic screening, why not have it done by highly competent professionals?

The answer to the second question comes down to how we approach the clinically unknown. If we have a test that produces lots of findings of undetermined clinical significance, then it seems ill-advised to throw up our hands and say that women shouldn't take the test because the results may be difficult to interpret. Wouldn't it make more sense to conduct some clinical research and learn something about these subtle lesions? We can't move forward by collecting anecdotal evidence; we need to examine data on hundreds of thousands of cases from the best mammographic labs. Then maybe we can start to design rational clinical trials where we look at how we can best deal with those lesions. I'm sure that among the small lesions found on mammography there will be lots of precancers. It would seem to me that mammographic screening in a young age group will give us the opportunity to develop effective and simple treatments for breast precancers (thus stopping the development of invasive cancer).

- © 2009 Jules J. Berman, Ph.D., M.D.

key words: mammographic, laboratory testing, screening test, mammography, breast examination, breast cancer, breast cancer screening, new recommendations, adverse effects of breast cancer screening, early cancer screening, cancer death rate, screening mammogram, screening mammography, new guidelines, new recommendations, task force recommendations, precancer, precancers

Thursday, November 19, 2009

New mammogram testing recommendations: an opportunity to cure precancer

In Yesterday's blog, I began a discussion of the new recommendation for mammographic breast cancer screening, announced by the United States Preventive Services Task Force (November 16).

The task force recommended that routine mammography screening begin at age 40, not age 50 (the previous recommendation).

The reason for the new recommendation relates to the low number of positive (malignant) cases in the 40-50 year age group and the high number of false-positives (nodules that are not invasive cancer) in the same age group.

I've been listening to a lot of discussion on TV and radio, and was surprised by the overwhelming (and strong) rejection of the new recommendation. Basically, it was just like any political issue: opponents rallying to reject the offered report, finding nothing of value and much to be reviled.

It seems to me that we stand to learn a lot from the task force's work, even if we don't follow their recommendation to the letter.

The problem with mammographic testing in young persons is that the test picks up small lesions that may be early invasive cancers, or they may be precancers (lesions that are not yet invasive cancers and that pose no immediate medical threat), or they may be lesions that mimic cancers but are actually benign disorders that have no medical consequence. When you look at younger and younger age groups (age groups not likely to have many invasive cancers), you pick up a disproportionate number of precancers and non-cancerous nodules.

The problem has been that these non-invasive lesions have been worked up by oncologists and surgeons with an array of surgical, diagnostic, and treatment interventions that have wasted money and caused great emotional distress in women who have not greatly benefited from the process.

Rather than drop testing, there are a number of options we could take, as a society, that might be better than the current way of doing things.

Radiologists could get together and develop diagnostic criteria for nodules that don't quite meet the criteria for malignancy. Radiologists and clinicians could then come up with recommendations for these nodules (e.g., repeat mammographic examination in 6 months, or 1 year, or whatever). Basically, the diagnosis and the recommended action would spare women from the mental, physical and economic consequences of an immediate cancer work-up.

Alternatively, the diagnosis of a "questionable" lesion could be used to qualify patients for inclusion in clinical trials for the treatment of precancers. Precancers are the non-invasive lesions that precede the development of invasive cancers. Precancers can be treated much more easily than cancers (this is the message developed in my recently published book, Precancer: The Beginning and the End of Cancer)Women with mammographic lesions consistent with precancer could be treated with experimental precancer treatments. If these treatments were found to be effective, we could greatly reduce, maybe eliminate, the breast cancer death rate.

The task force has made some important conclusions, based on their evaluation of the data. It would be a shame if we missed this opportunity to advance breast cancer treatment, simply because we don't like their final recommendation.

- © 2009 Jules J. Berman, Ph.D., M.D.

key words: mammographic, laboratory testing, screening test, mammography, breast examination, breast cancer, breast cancer screening, new recommendations, adverse effects of breast cancer screening, early cancer screening, cancer death rate, screening mammogram, screening mammography, new guidelines, new recommendations, task force recommendations, precancer, precancers

About my book, Precancer: The Beginning and the End of Cancer. Nearly every type of cancer passes through a precancer phase, during which it cannot metastasize or invade other tissues. While medicine is not always successful in treating or curing advanced stages of cancers, recent advances in our understanding of carcinogenesis have helped us to develop strategies to prevent, diagnose, and treat many cancers at the precancer stage. Research in this field is escalating rapidly as the evidence increasingly shows that the number of annual cancer deaths could be drastically reduced through the effective treatment and cure of precancer lesions. This book begins by explaining why it has been so difficult to cure cancers, followed by a review of precancer biology, with descriptions of the most common precancer lesions. The final chapters provide practical socio-political and medical goals for precancer treatment, including discussions of the economics and politics of treating precancers.



I urge you to read more about this important topic. Google Books has provided a generous preview of this book.

Wednesday, November 18, 2009

New mammogram recommendations

I'm sure that every reader of this blog has been following the news about the new mammogram recommendations, but if you haven't, you might want to read Gina Kolata's article in the New York Times. Basically, the new recommendation is for women to begin mammographic breast cancer screening at age 50, not at age 40 (the previous recommended age).

Like everyone else, I've been trying to digest this news. The fuss is based on a limitation that arises with all screening tests: Whenever you have a low incidence of disease in a population (as you have for breast cancer in younger women), it's hard to come up with a good screening tool that will catch all of the positive cases (high sensitivity), and pass on all the negative cases (high specificity). As you get a higher and higher natural incidence of disease in a population (as we have for breast cancer in older women), screening outcomes look better. The extreme example would be a disease that occurs in nearly 100% of the population. If you had a remarkably dumb screening test that called everyone positive, it would seldom be wrong for a population in which just about everyone has the disease.

When your screening test is flawed (as most are), it's always tough to draw a line in the population between those who benefit from the test and those who are harmed by the test.

The problem with mammographic screening is especially difficult because mammography is a complex, interpreted test. I'll explain what this means further on in this blog, but the upshot is that some labs can do mammographic breast cancer screeing much better than other labs. The high-performing labs may produce results that would prove highly beneficial to women in the 40-50 age range. The low-performing labs skew the national data and lead statisticians to think that screening is bad for this group of women, when the truth may be that only "bad" screening is bad.

A complex test is a test where lots of things can go wrong in the preparation of the test output. Was the patient positioned properly? Was the mammogram machine working properly and was it well-calibrated? Did the lab use the best possible mammographic equipment? Were the prior tests on the same patient made available for review and comparison with the current test? Was a proper history taken, to ensure that that radiologist had all the information needed to render the best possible diagnosis for the patient?

An interpreted test is one in which the output (the mammogram) needs to be rendered into a diagnosis. All interpreted tests can be misinterpreted. Some laboratories do a much better job at interpretation than others. The best labs have radiologists who are highly trained to diagnose mammograms, and who look at many mammograms, routinely. The radiologists should review the patient's prior mammograms, when relevant, and should read the relevant sections of the patient's history and physical examination. When a radiologist has a tough case, he/she should have a way of getting help from another radiologist. A good lab has records of these kinds of consultations, and can prove that they seek consultation on a reasonable number of cases.

Good labs have a system of quality controls over every aspect of the mammographic tests, and have a way of reviewing outcomes, so that a false negative or a false positive finding from the lab can be discussed by all of the laboratory personnel. In other words, does the lab have a method of knowing when they have made a mistake, and does the lab have a way of learning from the mistake?

Most importantly, a lab must be able to prove that it is a good lab. It should have a way of conducting quality checks on the diagnoses that come from the lab, comparing the different radiologists in the lab, and comparing their lab against other labs.

This is just a generalization, but my experience has been that there are vast differences in quality among screening laboratories. In the realm of my field (pathology), it has been shown again and again that large, high-volume labs tend to do much better with complex tests than labs that do only occasional testing.

So, the question that I have about mammographic screening is: has anyone determined whether there are ANY labs for which screening in the 40-50 year range is beneficial?

- © 2009 Jules J. Berman, Ph.D., M.D.

key words: mammographic, laboratory testing, screening test, mammography, breast examination, breast cancer, breast cancer screening, new recommendations, adverse effects of breast cancer screening, early cancer screening, cancer death rate, screening mammogram, screening mammography, new guidelines, new recommendations, task force recommendations

About my book, Precancer: The Beginning and the End of Cancer. Nearly every type of cancer passes through a precancer phase, during which it cannot metastasize or invade other tissues. While medicine is not always successful in treating or curing advanced stages of cancers, recent advances in our understanding of carcinogenesis have helped us to develop strategies to prevent, diagnose, and treat many cancers at the precancer stage. Research in this field is escalating rapidly as the evidence increasingly shows that the number of annual cancer deaths could be drastically reduced through the effective treatment and cure of precancer lesions. This book begins by explaining why it has been so difficult to cure cancers, followed by a review of precancer biology, with descriptions of the most common precancer lesions. The final chapters provide practical socio-political and medical goals for precancer treatment, including discussions of the economics and politics of treating precancers.



I urge you to read more about this important topic. Google Books has provided a generous preview of this book.

Monday, November 2, 2009

CHRONOLOGY UPDATED

I've recently made additions and modifications to my Chronology of Earthwebsite; a timeline of significant events, mostly scientific, in the history of earth; beginning with the big bang, followed 9 billion years later by the appearance of the solar system, and temporarily ending with all of us.

The chronology can be viewed at:

http://www.julesberman.info/chronos.htm

- Jules Berman

related words: world timeline, world time line, terran chronology, terrestrial chronology, chronology of science, timeline of science, science events, history of science, history of earth, science through history, science through the ages, science past and present, jules j berman
Science is not a collection of facts. Science is what facts teach us; what we can learn about our universe, and ourselves, by deductive thinking. From observations of the night sky, made without the aid of telescopes, we can deduce that the universe is expanding, that the universe is not infinitely old, and why black holes exist. Without resorting to experimentation or mathematical analysis, we can deduce that gravity is a curvature in space-time, that the particles that compose light have no mass, that there is a theoretical limit to the number of different elements in the universe, and that the earth is billions of years old. Likewise, simple observations on animals tell us much about the migration of continents, the evolutionary relationships among classes of animals, why the nuclei of cells contain our genetic material, why certain animals are long-lived, why the gestation period of humans is 9 months, and why some diseases are rare and other diseases are common. In “Armchair Science”, the reader is confronted with 129 scientific mysteries, in cosmology, particle physics, chemistry, biology, and medicine. Beginning with simple observations, step-by-step analyses guide the reader toward solutions that are sometimes startling, and always entertaining. “Armchair Science” is written for general readers who are curious about science, and who want to sharpen their deductive skills.