Tag Archives: health

A perfect death


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This week in which the country will come together to mourn the passing of a true American original, John McCain, it might be worth considering our (your) own mortality. Even as the ongoing progress toward controlling prostate cancer is underway, it remains clear that “something else” will get us. As an example, in a study I was privileged to lead among patients with high risk prostate cancer, other cancers (many of which were caused by our adjuvant mitoxantrone treatment) were as likely to lead to death and prostate cancer was the cause of dying only ~20% of the time

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As oncologists, we face the “end of life” issues more frequently than most physicians, and certainly deal with the reality of death more than folks in most other professions. I distinctly remember one lovely woman in her 50’s who was very open in discussing her wishes. She wanted to die while lying on her favorite beach in Florida watching the sunlight sparkling on the ocean – not an easy thing to arrange (and it didn’t happen). My own fantasy would be to have a lovely vacation in Hawaii (without this week’s rain) with my entire family, say my good-byes as I put them all on the plane, and stay over an extra day to pay for the hotel and be sure all of my financial affairs were up to date – then die of a heart attack on the way home the next day. Perfect. The airline would be carrying my carcass home for the mere cost of a coach seat and I wouldn’t even have to suffer that long in the crunched position with no leg room.

Short of these fantasies, however, I recently undertook an exercise that anyone could do and I herewith commend to you as well. My wife and I were lucky enough to score tickets to the London production of Hamilton last February. In it, there were two numbers that grabbed me by the heart. First was Washington’s “teach ’em how to say goodbye” song, “One Last Time”. As with John McCain’s final commentaries over the past few months, Hamilton’s farewell speech written for Washington was masterful (as is Lin-Manuel Miranda’s reprise).

But the song that most moved me to tears (and action) was “Who Lives, Who Dies, Who Tells Your Story”. After listening to it about a dozen times, I realized that we all have a story. It may not be as honest/noble as John McCain’s, or as consequential as Hamilton’s or Washington’s, but for some small group of your relatives or children or grandchildren, your story will have special meaning. If you don’t write it, your memories of your father, your grandfather, your family in general will die with you. In my case, I read a couple of autobiographies, self-published, from friends/acquaintances and decided that their stories were highly personal, and not terribly interesting. But when I started writing the story of my own grandfather and father, and my story, it was a joyful experience of reliving many happy memories, and a way of reconnecting with my first love affair, our children’s births, and the many blessings that have come my way. The result is not a literary masterpiece, but I am going to have it bound and give a copy to each of my kids to gather dust on their bookshelves.

In the arc of history, some things have not changed. “Our days may come to seventy years, or eighty, if our strength endures; yet the best of them are but trouble and sorrow, for they quickly pass, and we fly away.” (Psalm 90:10). Although trouble and sorrow are a part of life (and of dying), there can be real joy in pausing to appreciate all life has given you. Carpe diem!

 

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Filed under General Prostate Cancer Issues, Prostate cancer therapy

Of Prostates and Teslas


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If you thought this might be an article about how your urologist shops for his/her newest fancy car, you are mistaken (sadly…). Nikola Tesla was a fascinating inventor and ultimately “mad scientist” at the turn of the last century. Every time you plug your cuisinart into the wall to chop something up, you are the beneficiary of his contributions to the alternating current coming to your kitchen and the motor driving the chopper. My favorite story (because of the local connection) was his laboratory in Colorado Springs, where he attempted to develop a method of transmitting power without wires. By creating YUUUGE electromagnetic fields, he could make lots of electrical things happen at considerable distances, including knocking out the power station for the city. Here’s a quote from the Wikipedia article:

He produced artificial lightning, with discharges consisting of millions of volts and up to 135 feet (41 m) long.[11] Thunder from the released energy was heard 15 miles (24 km) away in Cripple Creek, Colorado. People walking along the street observed sparks jumping between their feet and the ground. Sparks sprang from water line taps when touched. Light bulbs within 100 feet (30 m) of the lab glowed even when turned off. Horses in a livery stable bolted from their stalls after receiving shocks through their metal shoes. Butterflies were electrified, swirling in circles with blue halos of St. Elmo’s fire around their wings.[12]

Of course, for purposes of this blog, the key thing is that the strength of magnetic fields was named after him. When you get an MRI of your prostate, brain, or anything else, you are put into a machine with a superconducting magnet that produces 1.5 or 3 “T” of strength. At the risk of being completely wrong and oversimplifying, what happens in the MRI machine is that a strong magnetic field temporarily lines up the hydrogen atoms in the water that is 70% of “you”, and when these atoms “relax” they give off radio signals that can be converted to images. Details and images are here. Early on, my colleagues and I were fascinated by the possibility of using MR to investigate the prostate gland and published an article (completely ignored – cited only 3 times, so must not have been that important…) showing changes in MR that occurred after testosterone administration to castrated rats.

Now there are complex MRI protocols to image the prostate using techniques I don’t fully understand (multiparametric imaging) that give us remarkable pictures of the prostate gland. Here is one:

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Prostate gland with red arrow indicating a suspicious lesion that could be biopsied or followed closely.

As with any radiologic imaging technique, the skill of the radiologist as well as the equipment being used determine the accuracy of the MRI to diagnose a cancer.

While most of us learned how to “read X-rays” in medical school, it is beyond most clinicians to read MRI’s of the prostate. Fortunately, the radiologists have developed a system that helps us think about “how abnormal” some area of the gland is, called PI-RADS.  This can be very useful in thinking about what area to concentrate on when biopsying a patient, or in trying to determine whether surgery or radiation therapy should be altered if there is concern that the cancer is outside of the gland. An interesting question that is still controversial is whether the MRI could replace repetitive biopsies in a man who has chosen active surveillance. Particularly when combined with molecular techniques (see my previous blog here) to characterize biopsies, it may be that Tesla will be helping to do more than get you from one place to another or run your electric shaver. (Rock on, Elon Musk) To me, that is a pretty interesting outcome from knocking out all of the lights in Colorado Springs!

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Filed under General Prostate Cancer Issues, Prostate cancer therapy, Targeted treatment

What is going to kill me? – the cloudy crystal ball


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With an intense focus on prostate cancer, it is easy to overlook the reality of other causes of death or disability in making decisions about therapy. An example of this issue is the proliferation of molecular tests that have been validated to separate patients with “intermediate risk”, or “low risk” into “even lower” or “even higher” risk disease categories using a number of different gene expression profiles on the tumor or biopsy material. For example, Genomic Health offers the Oncotype Dx test that provides a “Genomic Prostate Score” that gives a patient who (based on clinical criteria such as PSA and number of biopsy cores positive) falls into a low or intermediate risk category another lab value (GPS) that can potentially be useful in making a decision about treatment. GenomeDx has a test that can evaluate high risk men after prostatectomy to more accurately predict metastatic disease at 5 years. There is a very balanced article on the challenges of using these tests (which are a potential step forward to be sure) in the real world of the clinic here.

However, in all of the excitement and marketing of these and other tests, a couple of key facts are often overlooked (and may be much more important in decision making). Prostate cancer is generally a slow disease anyway. Competing mortality looms large as patients get older. And most importantly, there are validated ways to put the “whole patient” into the picture before ordering these tests, whether they be a PSA, biopsy, or molecular analysis. The Charlson comorbidity index can be extremely useful in predicting survival and is barely ever mentioned in the molecular analysis literature/reports. It is a simple yes/no answer to whether a patient has any of these 12 conditions: diabetes, bleeding gastrointestinal ulcer, chronic lung disease, congestive heart failure, stroke, myocardial infarction, angina or chest pain, cirrhosis or liver disease, arthritis, inflammatory bowel disease, hypertension, and depression. In a lovely article published last year, the use of this analysis in relationship to prostate cancer mortality gave a vivid picture of prostate cancer mortality in the larger setting of 3533 men with prostate cancer. A snapshot of their data looks like this:

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Very often, the comorbid conditions lead to death from another cause. In my opinion (and in my practice), we too often ignore our ability to quantify the risk of dying from “something else” when we focus so intensely on the PSA or other tests in counseling patients about what to do. It is also true that patient perception of test results can vary dramatically. One patient with a “GPS score” of 10 might be reassured, while another will perceive it as “not low enough” and opt for aggressive treatment rather than observation. To some extent this exposes the fallacy of “we need to separate the issue of treatment from that of diagnosis” thinking. Until the crystal ball becomes crystal clear, management of prostate cancer will remain challenging and requires the kind of wholistic thinking that is often better done by primary care physicians or public health professionals than by prostate cancer docs, or their patients.

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Lengthen your telomeres this week


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For journal club last week, I selected an article that looks at length of telomeres as a prognostic variable for prostate cancer. Telomeres are DNA protein complexes that are added to the tips of chromosomes by an enzyme, telomerase, that carries its own little RNA unit and was involved in one of the authors (Elizabeth Blackburn) of the story below winning a Nobel prize. As you get older, the length of your telomeres shortens, eventually giving rise to loss of important chromosomal information that can lead to cancer. In the journal club article, it was found that men who had shorter and more variable telomere length in their prostate cancer or the surrounding tissue, had a higher chance of developing metastases or dying from their disease. Of course this is bad news, and you might think there is nothing you can do about it. Not so fast….

Blackburn and her colleagues at UCSF have been studying men with prostate cancer to see if exercise and diet can influence telomere length. In a 2008 study, they found that peripheral blood cells had increased telomerase after 3 months of improved diet and exercise intervention. In their most recent study, they find that the continuation of the diet/exercise program results in actual increases in the telomere length in the peripheral blood cells. Since these are men with low risk prostate cancer who are being followed on a study with active surveillance, we will also be learning how such improved life style affects other genetic changes in serial biopsies of the cancers.

For now, the bet is that (as usual) you will benefit from increasing your exercise program, dropping red meat from your diet, and probably watching less football and doing more hiking this week with your family as you celebrate Thanksgiving. I’m just saying….

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Cow’s milk – not your father’s drink of choice?


When I was a kid, my father, having grown up on a farm, was obsessed with having me drink lots of milk. There was a milk delivery service in Chadron, NE, that brought rich, fresh, whole milk to our door, and I recall drinking at least a gallon a week – sometimes twice that. I was told it would “build strong bones and healthy teeth”, especially during my pubertal years, when there is of course a growth spurt that does indeed require more calcium and good nutrition. (Hence the increased height of American children over the past century…)

But there is a dark side to this story. In an article in Medscape today, there is a lovely review of another pathway that stimulates prostate cancer, namely one that involves the PI3K-Akt-mTORC1 pathway. It is way beyond this blog to try and go into this pathway in any detail, but suffice it to say that the authors present a powerful (albeit very long) argument that leucine, a branched chain amino acid found in high concentration in cow’s milk stimulates this pathway and can lead to prostate cancer growth and metastases. I will reproduce here (and without permission….I wonder if that is needed in the blog world…) a couple of the figures that illustrate the point. (note I am not plagiarizing since I give you the link to the original article containing these figures)

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This figure illustrates how leucine interacts with the signaling pathways that might lead to prostate cancer or stimulate its growth.

Screen Shot 2013-01-28 at 12.37.55 PMThis figure demonstrates the increased consumption of milk products like cheese and milk that have occurred over time in western countries.

The bottom line here is that milk and cheese have a dark side and we should probably curtail our intake, especially in families who have high prostate cancer rates. It would be nice to go into all 250+ articles the authors cite, but trust me, their arguments are very well founded. Too bad, since I love cheese so much !

 

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Screening (from a 30,000 foot view)


When you go through the screening systems at our national airports, there are often videos that describe the process, reminding you to take any liquids out of your suitcase and so forth. I think it is time for cancer centers (and others) to do the same thing at their annual screening events for breast, prostate and other cancers. I have no problem with participating in screening events if the participants are fully informed about the benefits, risks, and the controversies surrounding screening for prostate cancer. However without such information, I fear that most men simply open Pandora’s box without really knowing what they are getting into. Does a 75 year old man realize that his chances of dying from prostate cancer are tiny compared to the other lurking causes of death? Does a 60 year old man understand that a Gleason 6 cancer can be followed safely with active surveillance, but that it will require “life long” repetitive biopsies? The NEJM article on this issue this week is worth everyone reading. Marketing should not be what medicine is about.

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