I spend a lot of time trying to convince my patients to get screened for colorectal cancer. Somehow pap smears , mammograms, blood tests, urine tests and yes the occasional CT or even MRI scan seem doable and require little preparation (at least physiologically). But at the mention of a colonoscopy there is a reticence that seems universal. (After I write this I have to check to see if I am due for mine.) The New England Journal of Medicine presented a “Clinical Practice” article in its September 17th, 2009 issue. Since most of you don’t include this journal in your regular subscriptions (although it is currently available on Kindle) I though that it was a good time to go over the reasons for and methods available to screen for colorectal cancer.

Colorectal cancer is the second leading cause of cancer death in the United States. There will be approximately 147,000 newly diagnosed cases of colorectal cancer and 50,000 deaths from this disease in 2009. There is a gender difference and in women it is the third leading cause of cancer death, after lung cancer and breast cancer. The fact that it comes in third should in no way diminish our concern…remember very few men develop breast cancer. And if you wait for symptoms to occur, it may be too late to affect a cure….in many cases this disease strikes women who have no changes in their bowel habits!

Some of us may be at higher risk than others: If you have a first degree relative who had colorectal cancer before the age of 50 you may have an inborn genetic mutation that will predetermine a high risk for this cancer. There are gene tests (done as blood tests) that can ascertain if you have inherited colorectal cancer syndrome. If you are positive for these specific mutations, you will need very intense screening and perhaps surgery. If a first degree relative had this cancer at 50 years of age or older your lifetime risk doubles and screening should be started at 40 or 10 years younger than the age that your family member was diagnosed with this cancer. And if you have a history of chronic ulcerative colitis or colitis due to Crohn’s disease your risk increases and you should begin surveillance with colonoscopy 8 to 10 years after you received the diagnosis.

So now that we have established that colorectal cancer, like breast and cervical cancer requires screening; what are the stats on the success of the various methods? Let’s start with the “easiest”, the stool tests for occult (not visible to the naked eye) blood. Its advantage is that it can be done in the privacy of your home bathroom. There are 2 types of tests, the first requires 3 stool samples and is not specific for human hemoglobin. (You need to abstain from various foods , especially red meat). The second type may require just one annual stool sample. It specifically tests for human hemoglobin. If either test is positive, you will need follow up with a colonoscopy, to see what is there (causing the minute bleeding), and if necessary, a biopsy of a polyp or lesion to ascertain if it is cancerous or precancerous.. Persons with positive occult- blood tests have a risk of cancer that is 3 to 4 times higher than those with negative tests. The combination of annual stool test followed by colonoscopy probably picks up 50 to 75% of cancers…but there is no guarantee that these cancers are found at an early stage. Indeed if an advanced polyp that is destined to become cancer is present, the stool test for blood may be negative 50 to 80% of the time.     What I found interesting from a public health cost perspective (which will be factored into health care reform) is that the expense of screening with annual fecal blood tests, reminder systems and colonoscopy in patients with positive tests is just as costly as screening with colonoscopy!

There is a new stool test that may turn out to be more accurate than the one for occult blood. It detects specific DNA mutations from cancer cells excreted in the stool. The test is expensive and right now researchers don’t know how frequently it should be performed.  They also are not sure about the sensitivity of this test, i.e. whether it will pick up advanced, potentially precancerous adenomas.

Barium enema has been found to be inadequate for diagnosing precancerous lesions and is now rarely used for screening.

Now we come to the controversy surrounding CT imaging of the bowel. It, like colonoscopy requires complete bowel preparation (clear liquids for at least 24 hours, ingesting those diarrhea inducing solutions or pills and an evening spent near and on the toilet). Studies have shown that expert radiologists can identify 90% of polyps that are 10mm or larger.  But 14% of the time the “polyps” that they diagnose are not actually there when follow-up colonoscopy is performed (i.e. false positive). There also is a concern that the scan may not find flat polyps that can be cancerous or precancerous. The current estimate is that of all those who have this test, 15 to 25% will be referred for subsequent colonoscopy. (And remember this requires a second, unpleasant bowel prep!). Moreover, CT scan frequently does not demonstrate a polyp that is less than 6mm. At this diameter the polyp usually is not cancerous. However small can grow to large and the method of follow-up for small polyps presents a dilemma.

The radiation involved with these scans should also be factored in. Each scan may be fairly low dose, but if done repeatedly or other CT scans are done for other reasons, cumulative radiation can increase future risk of cancer. And finally, whenever scans are done, a lot of “needles in a haystack” may be found, often requiring invasive but ultimately unnecessary interventions. Up to 69% of persons who undergo screening with CT colon scans have at least one finding outside the colon. Studies show that further evaluation is performed in 5 to 16 % of persons who undergo this CT screening.

By now most of you realize that looking at just the lower portion of the colon with sigmoidoscopy is like doing a mammogram on one breast. This uncomfortable procedure (it requires enemas for preparation, and rectal insufflation with air) misses more than 30% of cancers that are present higher up in the colon…especially in women or patients over the age of 60.

Finally we get to the gold standard for colorectal cancer screening, colonoscopy. If you are screened (and have no known risk) you have a 0.5 to 1% chance of having colon cancer found with this test and a 5 to 10% chance of detection of advanced polyps that could become cancer and which can be removed at the time of the screening procedure.. This represents a huge (when in comes to cancer) window of opportunity to diagnose an impending “this can be bad” lesion and prevent cancer. Not only has a future disaster been averted, you are now classified as a polyp “grower” and you and your doctor know that you need to be followed with frequent screening.

As with any test, nothing is perfect. According to the New England Journal review article 2 to 12% of lesions that are 10 mm or larger in diameter may be missed during a colonoscopy. In order for the exam to be complete all the polyps that are seen should be removed. And “when colonoscopy is performed by properly trained endoscopists the risk of serious adverse events is 3 to 5 events per 1000 colonoscopies.” (This includes perforations and bleeding).

Colonoscopy affects every program because it is the last and most effective way to ensure that colorectal cancer is neither present nor impending. Guidelines from the American College of Gastroenterology recommend colonoscopy as the preferred screening test. If one or more polyps are found (which, if we include small polyps, occurs in 20 to 50% of patients), the interval for repeat colonoscopy varies according to the pathologic findings (usually between 1 and 5 years). I f no polyps are present and there are no risk factors, the colonoscopy can be repeated every 10 years.

There are two addendums to what I have just written. It appears that both black men and women develop polyps and colon cancer at a younger age and have a higher mortality from colorectal cancer than white individuals. So the current recommendation by The American College of Gastroenterology is to initiate screening in African Americans at the age of 45. And finally since even colonoscopy can miss the occasional polyp and recent studies show have shown that precancerous polyps can develop in less than 10 years, many gastroenterologists prefer to repeat colonoscopy every 7 years.

Well, this has certainly been a lengthy review. But after reading it I hope you don’t give your doctor or me that look of “you-must-be-kidding:” when we suggest you are due for your colonoscopy.  The colon you save may be your own!

Several times a week I receive a message from my nurse: “Ms.… called and is upset; she was informed by the mammogram center that she should return for additional views and an ultrasound”. Often the message goes on to say “She wants to know if she should go off her hormones?”

I can give my patients some general reassurance about these recalls. Up to 10% of women who undergo screening mammography are advised to return for additional imaging. That large percentage does not, however, suffice to allay the anxiety produced by this “your breasts warrant more scrutiny” report. What does help is informing my patients that 95% of these recalls are not associated with a diagnosis of breast cancer in the following year. (Remember screening involves annual mammograms, and a normal exam one year does not guarantee that the next will be as reassuring.)

What can make a mammogram difficult to read? Dense breasts probably rate as the number one tough-to- look-though-and-diagnose tissue and issue. The radiographer is searching for areas that appear solid or have certain kinds of spider-like calcifications that appear on x-ray as white against a fairly homogeneous black and gray background. But if the breast tissue contains densely packed glands with little fat between them the entire breast appears white on the image and it’s difficult to delineate bad white from good white. The younger we are the denser our breasts (They are also perkier!). Hence it’s particularly hard to diagnose an abnormal lesion with mammography imaging in a woman who is under the age of 40. Breast cancer is usually a cancer of longevity…which means the older we are the more likely we will develop this type of cancer. So at least we can reassure ourselves that as our age increases the “look-through” potential of our basic screening test improves.

Mammograms are only indicated in young women (before the age of 40) if they have a family member who has developed breast cancer before the age of 50, they themselves are known to have a mutation in the BRCA gene, they have had radiation to the chest wall before the age of 30 or, of course, if they present with a palpable mass. And in these young, high risk women, it is probably advisable to add ultrasound and in certain instances, an MRI.

There has been much ado over the fact that menopausal hormone therapy (HT) with estrogen and progestin is associated with an increase in breast density. And since dense breasts are more difficult to “read” (medically reported as a lower sensitivity and specificity), the question has been raised: should women go off their hormones one or two months before they have their mammogram? Would this help eliminate that 10% possibility of having to go through the anxiety, inconvenience and cost of additional tests?

A recent article in The Annals of Internal Medicine sought to answer this question. In a federally funded trial, investigators tried to recruit women who were using hormone therapy at the time of their screening mammograms and were then still using it when due for their next one. Of the 4,884 women who “qualified” for the study, two thirds declined to participate because they didn’t want to stop their HT use. (I guess the fear of developing hot flashes, night sweats or sleep disorders, even if temporary, overcame any desire to help research or potentially eliminate a difficult mammogram reading.) Those that agreed to participate were randomized to one of 3 groups; no suspension of HT, 1 month suspension or 2 months of suspension of HT before their screening mammography. The final study of willing participants included 1471 women, their mean age was 60 and 92% were Caucasian.

And what did they find?… Suspending hormone therapy had no impact on the recall rate. It was 11% for the no HT suspension group, 12% for the 1-month suspension group and 10% for those who went off their hormones for 2 months prior to their mammogram. Not surprisingly HT suspension was associated with a significantly greater likelihood of hot flashes (reported by half of the women at baseline and more than 85% of those who temporarily stopped their HT).

Bottom line: Stopping hormone therapy for a month or two before having a mammogram does not lower recall rates. Moreover, most women who are on HT are not willing to do this.

“I had surgery for an ovarian cyst”… a not uncommon statement in the medical histories I get from patients. This is usually followed by the exclamation: “Thank goodness it was benign!” The question is how many of these women underwent unnecessary surgery for something that was benign?

Most cysts in young women (we’re talking reproductive age here) are “functional”, a term used to describe furniture and clothes design…but when used as a gynecologic adjective it connotes a cyst that is formed during the monthly cycle. Follicular cysts develop as the ovary tries to do its duty and create a dominant follicle from one of its primordial oocytes during the first 2 weeks of the cycle. Once ovulation occurs a remnant of that follicle can form a second type of functional cyst termed a luteal cyst. Let me explain:

At the time of puberty the ovaries contain about 400,000 primordial or preformed oocytes (future eggs). Each month one of them usually gets to come forth to fulfill its destiny to grow and develop into a mature egg while thousand more die….sort of depressing, but this is the survival of the fittest egg. (Just consider how many sperm die with every ejaculate and perhaps you won’t feel so bad. But wait, sperm get produced anew every 3 month while we have a fixed number of eggs and once they are used up we can’t make anymore. So there is an ovarian woe in this saga. Our finite number of eggs also explains the hormonal phenomena of perimenopause and menopause, but I diverge…)

A small amount of fluid surrounds the developing egg so that the developed follicle becomes a little cyst on the outer circumference of the ovary. It produces estrogen. At ovulation the follicle ruptures and the egg is extruded. Some women feel this rupture as a mid-cycle pain called by the appropriate onomatopoeic term “mittlesmirz” (pain in the middle). If the cyst becomes large (too much fluid accumulates) and/or grows, it creates a functional follicular cyst.

Once the egg has been released (and potentially may be fertilized by sperm swimming in the tubal vicinity), the emptied follicle changes its identity and becomes a corpus luteum. This too is a small cyst that goes on to produce progesterone and estrogen; hormones that are needed to build up the lining of the uterus so that it can support a developing embryo. In the absence of a pregnancy the corpus luteum dwindles and yes dies; the uterine lining or endometrium is sloughed (the menstrual period) and the entire cycle starts all over again. But if that corpus luteum does not regress and instead swells or bleeds into itself (it has a terrific blood supply) it too can create a functional cyst called a luteal cyst.

Before ultrasound was extensively used, a woman who presented with a mass on the ovary, pain or an enlarged “something” in the area of the tubes or ovaries (called the adnexa), was often subjected to surgery. Even with the advent of ultrasound…if the cyst was big enough or had areas that were not translucent, surgery was often performed either by laparoscopy or an open abdominal procedure. The cyst was removed (cystectomy), or in some cases, the ovary was excised (oophorectomy). After all, the surgeon was already in there and that was the best way to ensure it would be properly diagnosed and “cured”. Any of these procedures could lead to subsequent scarring, pain and/or infertility.

In the 60’s and 70’s doctors noted that women who took oral contraceptives (in doses that were higher than those used today) seemed to have a lower incidence of these functional cysts. The thought was that if ovulation was suppressed there would be no reason for functional cysts to develop. (New data shows that low dose birth control pills do not substantially decrease a woman’s risk of ovarian cyst formation.) This theory that the Pill will stop cyst formation has continued to be used to treat cysts and make then “go away”.

Not so….according to a recent Cochran report that was abstracted in the Journal of the American College of Obstetricians and Gynecologists. The Cochran Review analyses the most relevant and well conducted studies that have been published in peer reviewed journals. The authors then review these studies for accuracy and statistical relevance. Seven randomized controlled trials from four countries were found; the studies included a total of 500 women. The analysis showed that “treatment with combined oral contraceptives (which contain both estrogen and progestin) did not hasten the resolution of functional ovarian cysts is any trial.” And indeed “most cysts resolved without treatment within a few cycles”. This included cysts that developed spontaneously and those that occurred after ovulation induction with fertility medications. (The forced feeding of the ovaries with fertility drugs causes the development of multiple follicles and can result in cysts). They found that most of the cysts that did not regress after a few months of being left alone were endometriomas (blood filled cysts that occur with the disease called endometriosis) or cysts that developed from the fallopian tubes.

So does your physician have to go after those cysts that she or he feels and then “sees” with ultrasound during routine exam? The answer in most circumstances is no. Nor do we have to treat these functional cysts with oral contraceptives to get rid of them. A simple “wait and recheck” in a 2 or 3 months is appropriate.

Bottom line: There is no need to freak at the mention of an ovarian cyst that has developed while you are in your reproductive years. It will probably go away in a month or two. Surgery is indicated only if you develop significant pain (very rarely cysts can twist or bleed) or if the cyst persists.

We rely on images to look into the presence or absence of disease. There are x-rays, ultrasounds, CT and MRI scans proffered by highly trained radiologists and technicians. But as they “see” into our bodies and render their official reports, their relevance has to be properly interpreted by the clinician and understood by the patient.

This is especially true for assessing the strength of our bones. By now most of us know about the test that has become the bone “gold standard”, the DEXA scan or duel-energy X-ray absorbtiometry. (Thank goodness we have an acronym.) Despite its long name this is one of the least scary radiologic tests available: You simply lie on an open table while fully clothed; an image of your hip and spine is made by a special scanner that travels the length of the table. The image then appears on a computer screen. (Fun to look at, at least for those of us that like this sort of thing…) A computer then calculates bone density based on the way the generated energy waves are absorbed by different areas of the bone. It’s rapid, taking less than 10 minutes, and the amount of radiation is minimal. Indeed, many physicians have the machine in their office….I usually refer patients to a radiologic facility, often the same one to which they go to for mammogram.

The results of the DEXA scan are given as a standard deviation (SD) from the average of the “ideal” women of your race who have reached their peak bone density in their early 30’s. (May I remind you that many of us didn’t get to that ideal bone density peak, especially if we did not consume the proper amount of milk and/or calcium, were not exposed to direct sun rays or given the right amount of Vitamin D as children and young adults and/or did not have appropriate estrogen during our reproductive years and as a result skipped our periods and of course, if we smoked!) This sometimes less than complimentary comparison is expressed as the T score. If you’re T score is minus one standard deviation, it means that your bones have sustained a bone density loss of 10% to 15% compared to the average for that ideal 30 year-old woman.

Osteoporosis has been defined by the World Health Organization as a bone density T score at or below -2.5 SD. The term osteopenia designates T scores between -1 and -2.5 SD’s. These are very arbitrary labels; a score of minus 2.5 or worse doesn’t mean that you will break your affected bone today or even in the future. Low or very low T scores represent a continuum of fracture risk that is also dependent on other risk factors. (One of the most important is the likelihood that you will fall.)

The current recommendation is that DEXA be performed on every woman after the age of 65. Many physicians order it for most of their post menopausal patients especially those not taking hormone therapies. I ask long term smokers, women who are at risk (see below), have underlying medical histories or take medication (such as steroids) that cause depletion of their bone density, to have this exam.

So what do we do with the results and are they sufficient to warrant mediation? A quick primer: bone is a living organ that is constantly being remodeled by bone drilling cells (osteoclasts) and bone filling cells (osteoblasts). The filling out paces the drilling as we build bones (up to the age of 30), after which the drilling is the more pervasive activity, causing bone loss and this becomes accelerated with loss of estrogen during and after the menopause transition. To build and maintain bone density we need appropriate amounts of calcium, Vitamin D and stress (through muscle action as we exercise and gravity as we stand erect). Most therapies diminish bone drilling so that the bone filling cells can do their job of filling in micro cavities. (These include estrogen and oral biphosphonates such as Fosomax, Actinol and Boniva as well as long acting intravenous medications).

In the past there was a general consensus (fostered by the pharmaceutical companies that produced these therapies), that the best bone defense was to start with a medication as soon as osteopenia was diagnosed, especially in post menopausal women who were not taking estrogen therapy. But follow-up studies have made it clear that there is no “free” bone strengthening, both in financial cost (most of the meds were expensive, although Fosomax has become generic and others are “on formulary” depending on the brand, the indication and the insurer) and potential side effects from long-term use. The reports of jaw bone necrosis leading to healing problems after major dental surgery have been well publicized. There are also case reports of the formation of unusually brittle bone which could lead to abnormal types of fractures. (Remember bone has to be remodeled to stay strong and supple; when the drilling is stopped and filling continues unabated, bone integrity may be compromised.)

I am finally coming to the reason for this report! There is a new assessment tool to improve analysis of your risk for developing an osteoporotic fracture over the next 10 years of your life. It may help us avoid diagnostic and therapeutic mistakes that may lead to premature and unnecessary therapy. It’s called FRAX. It is basically an interactive questionnaire that you and your doctor can answer. It estimates your 10 year probability of hip fracture alone and the 10 year probability of a major osteoporotic fracture at any one of four other potential fracture sites (your hip, wrist, the upper portion of your leg and your vertebrae).

The World Health Organization (WHO) has accessed data from more than 60,000 individuals and then calculated the relative risks for important risk factors as well as that of the density of bone in the hip. These were then used to help form the calculation for the FRAX assessment of your risk relative to the rest of the US population. It also adjusts for your gender, height and race/ethnicity.

FRAX is not a secret formula held in captivity by your health care provider. You can actually go online and estimate your own risk. It is available at www.sheffield.ac.uk/FRAX. It will ask you to fill in a “yes” or “no” or simply mark the appropriate box in order to calculate your risk for developing a fracture in the next 10 years. It also uses one of your DEXA calculations, but as only one of the factors and not one that should be solely considered. Your risk is calculated with the following questions:
• Gender
• Race/ethnicity
• Age (between 40 and 90 years)
• Weight (in kilograms and height in centimeters) which is used to calculate body mass index (BMI); a converter from metric units is provided in the margin of the website
• Family history: parents with a hip fracture (unfortunately this doesn’t take into consideration spinal fractures or severe Dowager’s hump)
• Personal history of fragility fracture after age 45 including fractures seen by x-ray only
• Use of corticosteroids: prednisone 5 mg daily or more for three months or longer, past or present
• History of rheumatoid arthritis
• Smoking: currently any amount
• Alcohol use: averaging more than three drinks a day
• Secondary osteoporosis due to: type I diabetes, untreated long-standing hyperthyroidism, lack of development of gonads, premature menopause, chronic malnutrition or malabsorption, organ transplant or chronic liver disease
• Bone mineral density either from the femoral neck T score, femoral neck bone mineral density or if only total hip BMD is available it can be used. (Note this tool is not designed to add the spine BMD into the calculations.)

The National Osteoporosis Foundation (NOF) has published new guidelines for diagnosis and therapy of osteoporosis. They concluded that if you take a biphosphonate for 5 to 10 years you can expect to reduce your fracture risk by about 35%. The NOF guidelines also use the FRAX 10-year risk results to recommend treatment in patients with osteopenia. They state that when the risk exceeds 3% or more for hip fracture and 20% or more for major osteoporotic fracture in the next 10 years, treatment is warranted. This helps take the guesswork out of deciding who qualifies for therapy when their T score is low.

Talk to your doctor (or if you are my patient, to me) if you have been taking a biphosphonate for more than 5 years. It may be time for a drug holiday. This type of medication may remain in the bone and inhibit bone resorption for up to an additional 5 years, so you’ll continue to receive much of its benefit subsequent to treatment. And before you start taking medication for low bone density, you and your physician should analyze whether it is even necessary. Your FRAX score may be more important than your actual bone mineral density score. We need all the support we can get.

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