Originally published in The Ottawa Citizen, August 6, 2005
Original Title: Sounds Like a Good Idea

New ultrasound technologies offer valuable diagnostic tools

The application of new technologies and research has the potential to revolutionize medical diagnostic imaging, diagnosis and treatment.

My last column looked at the amazing progress being made to restore lost sight. Exciting research and development is happening in the field of therapeutic ultrasound technology to treat prostate cancer and diagnostic ultrasound.

A new type of diagnostic ultrasound technology, reported in the April 16 issue of the New Scientist, is close to entering clinical trials. Dr. Vasilis Marmarelis, a professor of biomedical engineering, and his research team at the University of California’s Viterbi School of Engineering have created high-resolution ultrasonic transmission tomography (HUTT).

What makes the HUTT system different from conventional ultrasound is that it relies on the organs and tissue’s sound absorption qualities as opposed to sound reflection. Approximately 2,000 times as much sound passes through the organs and tissues than reflects back. Each tissue type absorbs a specific sound frequency akin to a “fingerprint” or sound biomarker. Dr. Marmarelis states that the system will be able to differentiate between benign and malignant tumours.

What is remarkable is that in addition to the ability to look at different structures with the same organ, the resolution is greater than magnetic resonance imaging. MRI images have a resolution of about two millimetres; it will image tumours or structures greater than two millimetres in size. MRIs take slices through the body like a stack of pancakes. Across the breadth of each pancake you have a two-millimetre resolution, but the space between the pancake layers is five millimetres.

The HUTT system resolves images as small as 0.4 millimetres across and between the slices, thus improving the image resolution. The rendered image is a smooth, high-resolution, three-dimensional picture. The machine appears similar to an MRI but, instead of lying down inside a drum, the patient remains standing.

The cost of the device is estimated to be five to 10 times less expensive than an MRI. Dr. Marmarelis is hopeful the HUTT system will become commercially available within 18 to 24 months.

Prostate cancer is the second most common malignancy in males worldwide. Men with early stages of prostate cancer now have another treatment option offered at the Don Mills Surgical Unit in Toronto. Although this treatment has been used in Europe for years, Toronto is the first city in North America to have this facility.

The treatment consists of using high-intensity focused ultrasound (HIFU) to destroy the tumour. The procedure can last between 90 minutes to three hours. A probe is inserted into the rectum after spinal or epidural anesthesia. It will image the gland and show the physician the location of the tumour in the prostate.

The probe will then emit sound waves that are focused into a tight beam targeting only the tumour. The focused beam heats the tumour to 85C, rapidly destroying the cancerous cells.

The HIFU system is indicated for men with stage T-1 or T-2 prostate cancer and for curative salvage therapy for local recurrence of the tumour after external beam radiation therapy. Studies are ongoing evaluating the long-term success rates of treatment.

The addition of new imaging software and technological improvements to the hardware continue to improve treatment outcomes.

One HIFU study done in Europe with 137 patients showed that 93 per cent had negative biopsies of the prostate gland five years after HIFU. Eighty-seven per cent had Prostatic Specific Antigen (PSA) levels of less than one microgram per litre five years after having the HIFU treatment. This evidence indicates a cancer-free state. Studies continue to follow these patients over the longer term. Retreatment rates are approximately 10 per cent.

Dr. John Warner, a Memorial Sloan-Kettering trained uro-oncologist practising in Vancouver, says HIFU is a clinically proven treatment for stage T-1 and T-2 tumours and is a revolutionary advance in their eradication.

The advantages to the patient are that it is non-invasive; there is no direct cutting into the tissue or ionizing radiation used, side effects are minimal, recovery is quick, there is less damage to the surrounding healthy tissue, and other treatment options can continue to be used to destroy the cancer.

Each patient is unique and requires special consideration. Consult your urologist about whether this would be an option for you. More information can be found on the website www.hifu.ca .

© Dr. Barry Dworkin 2005

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Originally published in The Ottawa Citizen September 20, 2004

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Originally published in The Ottawa Citizen September 20, 2004
Original Title: The Testes of Time

Young men rarely see their family doctor (if they have one). There is a tendency to think that nothing can really go wrong in your late teens or 20s.

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Originally published in The Ottawa Citizen October 15, 2003

Original Title: A review of letrozole therapy for breast cancer

The announcement last week that Letrozole reduced breast cancer recurrence represents another step forward in the battle against breast cancer. When an announcement of a “groundbreaking” study, it is understandable to react with hope that a cherished life will be saved and suffering will end.

Methodical evaluation of new research and treatments is critical to provide the public and health care professionals accurate information. Indeed, it is especially important when dealing with common diseases that touch the lives of many families and friends. Television and radio news, because of time constraints, cannot cover all the details and critical analysis of each medical study.

It is necessary to digress for a moment to define two terms integral to providing perspective to study results. Most studies will report disease reduction in one or two ways: relative and absolute difference. It is these terms that can be a source of confusion and misunderstanding.

Suppose a disease incidence in a particular group was initially two per cent and after treatment was reduced to one per cent. One could conclude that the incidence was cut by 50 per cent ((2-1)/2). This is relative difference. Since the rate dropped from two to one per cent, the absolute difference is one per cent (2-1).

The well-designed letrozole produced clinically relevant information. Important limitations of the study need addressing to provide a balanced view of the results. Two editorials in the November 6, 2003 issue of the New England Journal of Medicine (NEJM) reviewed the data with a critical and supportive eye.

In any study, the sample size (study population) must be great enough to provide statistically significant results. The letrozole study met this criterion by enrolling 5187 women eclipsing the minimum statistical requirement of 4800.

The study evaluated post menopausal women over the age of 50 years with estrogen receptor sensitive breast cancer. Each had recently completed five continuous years of Tamoxifen therapy. The investigators wanted to know if Letrozole, introduced following Tamoxifen therapy, would reduce breast cancer recurrence compared to women who did not take letrozole (the placebo group).

The length of the study was to last five years. It was halted at 2.4 years because the reduction in breast cancer recurrence exceeded their expectations. It was decided that it would be unethical to withhold this treatment from the placebo group.

Of the 5157 women, 75 out of 2575 (2.9 per cent) in the Letrozole group and 132 of the 2582 women (5.1 per cent) in the placebo group had a recurrence of their breast cancer. In other words, 57 fewer women compared to placebo developed breast cancer. This result was reported as a 43 per cent relative reduction ((132-75)/132).

The absolute reduction of breast cancer is somewhat different. Indeed, Dr. Harold J. Burstein in a NEJM editorial states, “To date, letrozole has reduced the aggregate number of recurrences of breast cancers from 5.1 per cent to 2.9 percent-a reduction of approximately 1 event per 100 women treated per year.” The one in 100 statistic is calculated by dividing the absolute reduction of 2.2 per cent (2.2 women per 100 women) by 2.4 years.

The study presents other limitations. The investigators admit the lack of a true five-year duration makes it difficult to project the long-term consequences of letrozole treatment. At best the study’s conclusions reflect only two to three years of Letrozole treatment.

It is difficult to extrapolate the information past three years. Indeed, the stated objective of the trial was “to determine the disease-free survival and overall survival for women who has previously received = 5 years of adjuvant (tamoxifen) randomized to receive either letrozole 2.5 mg daily or placebo for five years.”

Overall survival was not significantly different after two years between the placebo and letrozole group. Extrapolation of the data into the third and fourth years indicates five to six per cent more women in the letrozole group would have survived.

John Bryant, Ph. D. and Dr. Norman Wolmark in their NEJM editorial comment that these findings cannot “be used to support a recommendation of five years of letrozole treatment, since none of the patients have been followed that long.”

They further state that the long term safety of this medication with respect to heart and bone health and quality of life could not be determined. Letrozole blocks the production of estrogen. It is associated with the development of osteoporosis, hot flashes, night sweats, muscle ache, arthritis, osteoporotic fractures, potential cardiovascular disease and impaired sexual function.

It is therefore difficult to make clinically appropriate judgments about the risks versus the benefits of the treatment when the full extent of its side effects and efficacy remains unknown.

As with other treatments, time, experience and more clinical trials will help answer some of the unknowns. Letrozole is an option for specific patients but they must be apprised of the limitations of the data. It is imperative that post menopausal women with estrogen receptor sensitive breast cancer discuss her options with her oncologist.

© Dr. Barry Dworkin 2003

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Originally published in The Ottawa Citizen August 5, 2003
Original Title: BPH, PRCa, PSA:What’s the deal?

CJOH anchor Max Keeping’s selfless revelation about his prostate cancer has renewed interest in prostate disease and PSA testing. His announcement came the day after a group called Early Prostate Cancer Diagnosis launched a campaign geared at getting OHIP to pay for an the early screening called the prostate-specific antigen (PSA) blood test for all men over 40.

As it stands, the province will fund PSA tests for men who have already been diagnosed with prostate cancer and those who already have symptoms.

But diagnosing prostate cancer is sometimes no simple matter, even with the PSA test. Is it worthwhile to find the $25 in your own pocket for the peace of mind?

One thing that make prostate cancer hard to diagnose is that it has symptoms similar to those of other conditions, including benign prostatic hypertrophy (BPH), which usually starts after the age of 50.

This enlargement of the prostate gland can cause significant discomfort and potential bladder damage. The prostate increases in size in eight per cent of men aged 31 to 40, in 40 to 50 per cent of men aged 51 to 60, and over 80 per cent of men older than 80 years of age.

If you are a man and live to a ripe old age, chances are good you will get prostate cancer. You’re also very likely to survive it.

Autopsy studies show 10 per cent of men over 50 had prostate cancer, while 70 per cent of men over 80 had it. Ten per cent of prostate cancer is inherited. One in nine Canadian men will get prostate cancer and one in 29 will die of it.

The symptoms of BPH and prostate cancer slowly develop over years. The signs include getting up more frequently at night to urinate, needing to void after urinating, waiting longer for urinary flow to begin, dribbling after urination, urinating more often during the day and a slower, less forceful and sputtering urinary stream.

BPH and prostate cancer have the potential to obstruct the bladder’s efforts to empty. Urine accumulates and distends the bladder walls, which can permanently damage bladder function. It loses the ability to contract and expel the urine.

But other disorders can also be at fault, including a narrowing of the urethra (the tube running from the bladder to the tip of the penis) or the bladder outlet, bladder cancer, bladder stones, urinary tract and prostate infections, or poor nervous system control of the bladder.

A thorough medical history of urinary difficulties, nerve damage or disease, bloody urine, trauma to the urethra and medication use helps point the way to a specific diagnosis.

Rectal examinations will help assess prostate size and consistency among other characteristics and differentiate between benign versus malignant disease.

Several other tests will complement the evaluation, ranging from a simple urine test for blood and infection to more invasive procedures.

A common imaging test, a transrectal prostatic ultrasound, will determine the size of the gland, its consistency and if there are suspicious areas for prostate cancer.

Other tests will measure how well the bladder functions. If there is a clinical suspicion of prostate cancer, a prostate biopsy would be the next step.

BPH treatment involves lifelong medical therapy and, depending upon the clinical situation, surgery to remove part or all of the gland.

Prostate cancer treatment includes a combination of chemotherapy, surgery and radiation therapy. Early detection is essential.

There is contradictory and confusing information about the PSA test. Still, it remains a valuable tool especially for certain clinical conditions, race and age groups.

PSA is a protein produced by the prostate gland. Most of it is attached to other blood proteins, but some floats freely in the blood stream, not bound to other substances.

This unbound type, “free” PSA, is low in men with prostate cancer and high in men with BPH. The serum PSA test adds the bound and free PSA levels together.

PSA levels increase with gland enlargement. The test can be used as a cancer-screening tool for men between 50 and 69 years of age because of the predictable slow and steady growth of the gland and PSA values.

However, the PSA test has limitations, in part because of other influences on the prostate gland. Irritation, ejaculation, infection, obstruction of the urethra and direct pressure (from a rectal exam or anal intercourse) will pump more PSA into the bloodstream, artificially elevating the result.

Men over the age of 69 tend to have more rapid enlargement of the prostate and increasing PSA levels. The results must be interpreted according to age and race-based normal values. Failure to do so could lead to false positive or negative results.

The widely used cut-off serum PSA value of four nanograms per millilitre, an indicator for the suspicion of prostate cancer, remains controversial.

Recent evidence indicates lesser values being associated with cancer. In three studies of men aged 50 and older, 148 of 597 men without prostate cancer (25 per cent) had a PSA value of four or higher. And 136 of 319 men with prostate cancer (43 per cent) had values below four.

A “free” PSA test — a variant of the PSA test — might improve cancer-screening evaluation. This test measures the individual concentration of the total PSA and free PSA. The total PSA level must be more than four in order for this test, combined with the patient’s age, to differentiate BPH from prostate cancer.

To date, the evidence indicates a combination of digital rectal examination and serum PSA testing is the best available means to exclude prostate cancer. The recommendation is to start screening for prostate cancer by age 50 with a rectal exam and PSA.

Family history might result in earlier testing, say, at around age 40. Given the evidence that this is the best we have so far, it stands to reason to give men any opportunity to prevent the disease.

Every other test we have that is covered by OHIP has no age restriction. I do not think PSA should be subjected to this rule. The decision for the test is based on clinical interpretation of the facts and in the best interest of the patient. There must be consistency in the system.

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Originally published in The Ottawa Citizen May 7, 2002
Original Title: Irradiate My Soul and Thanks for the Tan

With the summer months approaching, the ozone hole growing and the tan enthusiasts ready to hit the beach, it is important to know how skin valiantly tries to protect itself. Alas, people subject their dermis (skin) to multitudes of insults and injuries. Cuts, bruises, scrapes and mild burns heal well and cause no lasting damage. Ultraviolet radiation (UV) is less forgiving.

Skin will tan to create a protective shield in response to UV exposure. The darker the tan, the less UV will be able to penetrate through the skin. There are three UV wavelengths, UVA I, UVA II and UVB. The latter two wavelengths are the major cause of sunburn. UVB is more damaging to skin because of its deeper skin penetration. UV damages or mutates the skin’s DNA, causes pigment changes, wrinkling and loss of skin elasticity. Skin pigment cells (melanocytes) can mutate and become cancerous.

Even though the tan may fade over the winter, the UV effect upon the skin is permanent. The damage is cumulative. Repeat sunburns and regular exposure to tanning beds among other factors continues the cycle of DNA damage. Skin will prematurely age becoming leathery and lose its suppleness.

The most serious skin cancer is malignant melanoma. It accounts for 75% of all deaths due to skin cancer. It is responsible for one to two percent of all cancer deaths in North America. In 1960, the lifetime risk of developing melanoma was one in 1500. By 2000, the risk stood at one in 70. The incidence of melanoma has doubled in the past decade mostly in people between 20 to 45 years of age. It ranks seventh in cancer incidence for females and sixth for males. Death rates are increasing by two percent per year. Survival rate are improving as well.

The greatest risk factors for melanoma are a history of a changing mole, a family history of melanoma and a personal history of having melanoma.

Since 80% of lifetime sun exposure occurs before age 18, a person’s skin type plays a role in their skin cancer risk. People with very dark or black skin rarely experience sunburn. There are four sun-reactive skin types for people with white skin.

People with Type I skin never tan and always sunburn. Those with Type II tan less than average, have difficulty tanning and usually burn. Both types tend to be found in people with pale skin, red or blond hair, blue eyes, freckles and who are of Celtic ancestry. Some people with dark brown hair and blue/green eyes are included in this category. The majority of people have Type III skin. Their skin tans about average and only sometimes does it mildly burn. Indeed, this group also is most likely to have a history of deliberately prolonged or repeated sun exposure in order to obtain a cosmetic tan.

Type IV skin rarely burns and is generally seen in people with dark swarthy skin. It easily tans and is the least likely to become cancerous.

Early detection and consistent use of sunscreens is the best means of preventing skin cancer. If you are concerned about the appearance of a mole on your skin the following ‘ABCDE’ criteria for melanoma risk may be helpful:

• Asymmetry: If the mole is divided in half by an imaginary line, both halves should appear identical for a non-cancerous (benign) mole.
  Borders: The benign mole is usually round having sharp well-defined margins. A ragged or uneven border is not normal.
• Colour: A mole having a homogenous brown colour is normal. Multishaded moles or those that have a combination of colours such as blue, purple, red or black are suspicious for cancerous change.
• Diameter: Moles greater than 6 millimetres (~3/8 inch) in diameter, about the size of a pencil eraser, are suggestive of melanoma.
• Enlargement: A recent increase in the size of the mole warrants further investigation.

Any abnormal finding should be seen by your doctor. Some of the signs of non-melanoma skin cancers include: Red, flaky, itchy irritated patches, ulcers that do not heal in two weeks, areas of skin that keep cracking and bleeding or become rough, red and bumpy. Check your skin at six-month intervals. Skin cancers grow slowly. Many people in Canada have a childhood history of many sunburns while swimming or doing outside sports or chores. They particularly need to be careful about further exposure.

Sunblock, protective clothing, caps, hats and UV-blocking sunglasses are the mainstays of prevention. Choose a UVA and B sunblock that has a sun-protection-factor (SPF) of at least 15. Using sunblock can lead people to get more exposure because of a false sense of protection. The best protection is to not spend too much time outdoors when the summertime sun is highest and hottest (between 10 AM and 4 PM). Using an awning for a children’s play area or an area where you sit outside and read adds an additional layer of protection to your hat and clothing. UV comes through the clouds so a cloudy day offers little protection.

Reduce your exposure to pesticides and herbicides containing organic arsenic. These compounds increase the risk of skin cancer. Tanning booths, claims to the contrary, irradiate the body with skin-damaging UV to stimulate the tanning process.

The goal is to avoid UV radiation exposure and sunburn. No one wants skin that looks better on alligators or Komodo Dragons.

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Originally published in The Ottawa Citizen July 17, 2001

Mr. H., a World War II veteran was posted 24 times in 27 years while serving in the Canadian Armed Forces. He is proud of his accomplishments and his actions demonstrate quiet dignity and honor. He has told me stories of his military life. Stories about sacrifice, dedication, honor and integrity that children, not to mention some adults should hear. Now, at age 78 I have told him he has inoperable kidney cancer because it has spread to his lungs. He would not survive the operation.

We talk openly about palliative care and his funeral arrangements. He discusses it in a matter of fact way. He has prepared himself and set his affairs in order. His eyes betray great sadness and fear. He is a man without a family. He never married. His friends are gone. He is alone. He talks to my patients in the waiting room. One patient asks me if he is okay. He is “such a sweet man” she says, “but he looks so lost and alone.”

As he limps into my office, cane in hand, I wish I could change his future. The unfairness of life once again is cruelly played out upon those who have sacrificed the most. This man helped protect our country. And he is already forgotten. His wish is to die in a veteran’s hospital. This is arranged but he hopes they can accept him in time with the waiting lists such as they are. His pain is noticeably worse but he refuses pain relief for now. My nurses and I offer him whatever help he needs. Despite the rationing of care now-a-days, he is grateful for what he has received. This man deserves better but he would never say so.

Last March at the Ottawa General Hospital, I had the privilege of meeting Mr. R., a strong, independent fifty six year old man admitted to our family medicine service. Five weeks earlier he was on a “trip of a lifetime” cruise with his wife. After the trip he went to see his doctor because of fatigue. Two weeks later he was hospitalized for liver failure due to spreading cancer. His family was devastated. There was no warning, no time to prepare themselves. His liver could not produce the protein his body needed to keep water in his blood vessels. Everyday fluid would leak into his abdomen, legs, hands and lungs. He would always be thirsty. But the more water he drank, the more bloated he would become. Each day his lungs would fill up just a little bit more with fluid. His breathing became more labored, his skin more yellowed. Toxins that normally would be neutralized accumulated in his body.

He was a man losing control of his life, a completely new and frightening experience for him. Yet, he wanted to be in control to the very end. He wanted to know how he was going to die. He asked the dreaded question, “How much time do I have?” The residents and I answered all his questions. He had about 2 to 6 weeks to live. We were determined that he would die with honor and dignity. We talked about pain control and that he should be comfortable. His family wanted a private room so they could personalize it for him. We shook hands. When we left the room one of the residents burst into tears. I cannot imagine someone I hardly know telling me I am about to die a horrible death in front of my family.

He resigned himself to his fate. Instead of withdrawing he spent the rest of his days telling his family how much he loved them and how proud he was of his children. His family remained with him. Seven days later he died. His family was with him until the end.

I am truly privileged to have met these courageous and selfless men. Facing the ultimate fear they demonstrate the strength of the human spirit. One alone and in silence, the other more concerned for the well being of his wife and children and dying in the loving embrace of his family. At the end of one’s days all that one has is dignity, honor and respect. I have seen many throw their souls away for the most trivial of reasons. My fear of the slow decline of these societal values is somewhat eased when I meet people such as Mr. H and Mr. R.

Right after seeing Mr. H., a beautiful sweet 2 year old girl comes into the office with her mother who is expecting her second child. The girl has that high-pitched voice that just melts your heart. I balance her upon my knee so she can hold the Doppler to her mother’s abdomen to hear the baby’s heart beat. She is so happy. Her world is wondrous.

From life to death, from innocence to life’s final destiny and all the experiences in-between— all in one day. Teach your children well.

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