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Other, Oral Targeted Cancer Treatments

Some of you may be wondering why I’m so fixated on oral, targeted therapies for cancer. In my last post I provided some information on nine cancer drugs aimed at cellular enzymes, or kinases.

I’m encouraged, first, by the rapidity of these drugs’ emergence: ten years ago, none of the kinase-blocking drugs were available except for a few in experimental trials; most received FDA approval only in the past five years. These are very new agents indeed.

Why I’m enthusiastic – I anticipate that within a few years from now, cancer patients will take “medication cocktails” for their tumors, much in the way people living with HIV use drug combinations to fend off infection.  Cancer will, in many circumstances now deemed incurable, be managed instead as a chronic disease.

Now I can complete my assignment – a list of current, oral FDA-approved targeted cancer therapies. As indicated previously, I’m not including hormonal treatments in this list. I considered oral drugs targeting kinases in the last post.

I should emphasize that I’m neither recommending nor advocating any particular drugs. Rather, my point is to demonstrate the evolution of the field, that so many new and varied types of cancer pills are available. I think this is the start of a new era in oncology with expanded treatment options for people with all kinds of malignancy.

Part II of FDA-approved Oral Targeted Treatments for Cancer (see also part I – on oral kinase inhibitors)

1. Zolinza (vorinostat) is FDA-approved for use in a few forms of lymphoma that are cutaneous T cell lymphoma (CTCL). These are non-Hodgkin’s lymphomas in which the malignant cells are T-lymphocytes infiltrating the skin.

How this agent works is by inhibiting histone deacetyalases. These enzymes act in the cell’s nucleus, or center, where lies the DNA strung out along chromosomes. It removes acetyl groups, small chemical structures, from histone proteins. The genetic material normally wraps around the histones, and the presence or absence of acetyl groups on histones affects how genes are turned on or off. (Merck, October 2006).

2. Targretin (bexarotene) comes in capsule and in gel forms. It’s a retinoid, a Vitamin A-like compound that binds retinoid X receptors. These receptors regulate gene expression in normal and malignant cells. The drug is FDA-approved for use in CTCL. (Ligand, now Eisai, December 1999).

3. Vesanoid (tretinoin) is a retinoid that binds retinoic acid receptors. This drug is approved by the FDA as part of the treatment regimen for a particular form of leukemia called acute promyelocytic leukemia (APL). The drug targets a retinoic acid receptor that’s abnormally produced in the malignant cells due to a disease-defining chromosomal switch involving the retinoic acid receptor alpha (Roche, and generic, 1995)

This list is derived, in part, from information on the National Cancer Institute website on targeted cancer therapies, supplemented by other public-access resources on the relevant drugs and molecules as I’ve indicated with relevant links.

Some comments:

In this review, I note that some drugs that are not conceptually distinct from conventional chemotherapy or hormonal treatment appear to be marketed as “targeted” cancer treatment. My concern is that some companies are using this term, which implies a scalpel-like effectiveness and selectivity, to sell drugs to patients and oncologists (who may not all be up on their kinases) regardless of the drugs’ real specificity or lack thereof.

Given that all cancer drugs are designed, in principle, to kill malignant cells without killing the person who has cancer, we might consider all anti-tumor drugs as “targeted therapy.” But I don’t think that would be reasonable or helpful to patients and physicians who are trying to distinguish among treatment options.

In my opinion, the “targeted” term should apply only to drugs that impede troublesome molecules that act up particularly in the malignant cells, such as the bcr-abl tyrosine kinase mentioned in the last post, or the altered retinoic acid receptor that’s implicated in APL, as considered above.

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Some Targeted Therapies for Cancer Come as Pills

This post, on FDA-approved small-molecule targeted therapies for cancer, seems like a homework assignment of sorts. But really I found it a useful exercise and hope some readers might find it so, too. In searching the Web, I found remarkably little on this that’s public-domain, comprehensive and organized. In fact, there seems to be a lot of confusion about what these drugs are and how these differ from conventional, cytotoxic chemotherapies.

Some historical perspective:

Before 1970, few people received chemotherapy. Even with a cancer diagnosis, most treatments were surgical and radiation-based. A few older agents, chemotherapy pills such as chlorambucil and melphalan were given by mouth. From 1970 until 2000 (more or less), the thrust of most new cancer treatments involved stronger and sometimes more effective combination chemotherapy regimens. Almost all of those new treatments were given by intravenous (IV).

One point here that’s relevant to health care reform and the current debate on physician payments is that as things stand, oncologists and medical centers make money by giving IV infusions. Each treatment is billed as a procedure, apart from the cost of the medication in itself. So if patients can take a drug without a catheter, it might be less costly – there’s no nurse to hire, no catheter to purchase and insert and there’s no billing for an infusion per se.

And there’s less cost to the patient in terms of hassle and some untoward effects of IV treatment. With oral drugs (capsules, pills or tablets – anything taken by mouth) there’s no need to go to the doctor’s office or medical center every week or every other week, or even daily as is prescribed for some chemo regimens. There’s no need to have one’s arms shot up or a permanent, dangling catheter inserted. There’s no attendant risk for infection from an IV or semi-permanent catheter.

Reality check: most effective cancer drugs are not available in pill form, and for the most part these targeted treatments are in their infancy. But their number is expanding, so much so that most of the cancer pills I’m about to list have been approved only in the past five years.

Take further note: these are toxic drugs. Targeted therapies are designed, in principle, to kill malignant cells while leaving normal, healthy cells alone. Unfortunately, the effects of the medications listed below are broader than would be ideal. In general, these pills take aim at molecules that are over-active in cancer cells. But most of the affected enzymes are present in regular, healthy cells, too.

Here’s a list of small-molecule, oral drugs that target cancer cell enzymes and have received Food and Drug Administration approval prior to March 9, 2010, in order of approval:

1. Gleevec (imatinib, STI-571) was the first drug in this class to receive FDA approval. It counteracts an abnormal enzyme, a tyrosine kinase, that’s active in chronic myelogenous leukemia (CML) cells. The malignant tyrosine kinase, bcr-abl, arises in most cases from a chromosomal switch, called the Philadelphia Chromosome.

It turns out this drug works, also, against another tyrosine kinase, one related to a cell surface receptor protein called c-kit that’s mutated and activated in many Gastrointestinal Stromal Tumors (GIST). In 2002 the FDA approved use of Gleevec for GIST tumors in “c-kit+” tumors, meaning GIST cancers in which the c-kit receptor is mutated.

Since then the drug’s been approved for additional uses, only in some and quite specific circumstances, for adults with acute lymphoblastic leukemia (ALL) in which the malignant cells harbor the Philadelphia Chromosome (Ph+) and for some patients with other, mainly rare blood disorders in which particular genetic changes are established. (Novartis, May 2001)

2. Tarceva (erlotinib). This drug is also a tyrosine kinase inhibitor and is thought to act primarily by blocking growth signals of the Epidermal Growth Factor Receptor (EGFR). The drug was initially approved for use in some patients with non-small cell lung cancer and, more recently, for patients with pancreatic cancer. (Genentech, November 2004)

(Here I should mention Iressa (gefitinib) that was approved by the FDA early on for treatment of patients with advanced non-small lung cancer. Like Tarceva, Iressa has activity against EGFR-linked kinase activity and growth signals. The drug is no longer approved for most patients. AstraZeneca, 2003)

3. Sprycel (dasatinib). Like Gleevec, this targeted therapy blocks the bcr-abl tyrosine kinase activity in CML. The FDA approved this medication for CML patients whose disease progressed while on Gleevec (Gleevec-refractory CML) and for some adults with ALL in whom the malignant cells are Ph+. (Bristol-Myers Squibb, June 2006)

4. Sutent (sunitinib). Sutent is approved for use in metastatic kidney cancer and in GIST tumors that have progressed during treatment with Gleevec. It’s a fairly broad-acting tyrosine kinase inhibitor. (Pfizer, January 2006)

5. Tykerb (lapatinib). Tykerb is the only small-molecule drug that’s FDA-approved for use in some breast cancer cases. It blocks growth signals through Her2 (Her2/neu), a receptor tyrosine kinase that’s present on the surface of some breast cancer cells. The drug is approved for patients with metastatic breast cancer that’s Her2+ (meaning that the malignant cells display this molecule) and when it’s given in combination with Xeloda (capecitabine, an oral version of an otherwise conventional chemotherapy).

In January of 2010, the FDA granted accelerated approval of Tykerb in conjunction with Femara (letrozole, a hormonal therapy) in some patients with metastatic, Her2+ breast cancer in which the cells also express estrogen and/or progesterone receptors. (GlaxoSmithKline, March 2007)

6. Tasigna (nilotinib). This is the latest drug to tackle the bcr-abl tyrosine kinase activity in CML. It’s approved for adults with CML who have failed at least one regimen containing Gleevec. (Novartis, October 2007).

7. Nexavar (sorafenib). This therapy may not be targeted in the truest sense because its activity is so broad. It blocks receptor-linked tyrosine kinases such as those associated with Vascular Endothelial Growth Factor Receptor (VEGF-R) and Platelet Derived Growth Factor Receptor (PDGF-R). It inhibits other types of signaling enzymes inside cells, such as Raf-associated serine-threonine kinases.

The FDA has approved this drug for two groups of patients: those with advanced renal cell (kidney) cancer and those with liver tumors that can’t be removed by surgery.  (Bayer, November 2007)

8. Afinitor (everolimus) is in a slightly different class of drugs, in that it blocks mTOR (mammalian target of rapamycin, another sort of cellular enzyme). This drug is approved for use in patients with metastatic kidney cancer whose disease has progressed after Sutent and Nexavar. (Novartis, March 2009)

9. Votrient (pazopanib) blocks numerous tyrosine kinases and is the latest FDA-approved drug in this class. It’s approved for patients with advanced renal cell (kidney) cancer. (GlaxoSmithKline, October 2009)

Note to readers: other, oral targeted therapies are available that act by different sorts of mechanisms. I will cover those separately.

Several websites provide more information on so-called targeted therapies for cancer, including new intravenous treatments, monoclonal antibodies and some drugs that act by distinct mechanisms. Some of the sites I recommend for this topic include the National Cancer Institute and the American Society of Clinical Oncology’s Cancer.Net.

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Considering Targeted Therapies For Cancer

I first heard about STI-571 (Gleevec, a targeted cancer therapy) from a cab driver in New Orleans in 1999. “Some of the doctors told me there’s a new cure for leukemia,” he mentioned.

We were stuck in traffic somewhere between the airport and the now-unforgettable convention center. His prior fare, a group of physicians in town for the American Society of Hematology’s annual meeting, spoke highly of a promising new treatment. It seemed as if he wanted my opinion, to know if it were true. Indeed, Dr. Brian Druker gave a landmark plenary presentation on the effectiveness of STI-571 in patients with chronic myelogenous leukemia (CML) at the conference. I was aware of the study findings.

“Yes,” I said. “There is a new drug for leukemia.”

Since then, oncologists’ enthusiasm for targeted therapies – medications designed to fight cancer directly and specifically – has largely held. But the public’s enthusiasm is less apparent. Perhaps that’s because many people are unaware of these new drugs’ potential, or they’re put off by their hefty price tags.

Today Bloomberg News features a detailed and, I think, thoughtful story on the high cost of Sutent (sunitinib malate). This “miracle drug,” similar in many ways to Gleevec, typifies the problem of developing and providing new targeted therapies for patients with cancer. Sutent costs as much as $200 per pill, amounting to almost $50,000 per year for those who benefit. But the drug helps only a fraction of the patients for whom it’s prescribed.

So I thought I might review targeted cancer therapies, the costs-benefits issue being real and relevant. N.B.: addressing these drugs’ relative merits, effectiveness and side effects is beyond the scope of this blog. Rather, I’ll try to provide a simple framework for understanding these drugs, some information on the distinct types of new treatments and how these might work to fight cancer.

First, the framework: although many news articles consider targeted therapies together, I’d divide these in three main classes:

1. Enzyme Inhibitors. These drugs, most of which are available as pills, are designed to inhibit specific, abnormally-active signaling molecules in cancer cells. Gleevec was the first of this sort of therapy approved by the Food and Drug Administration.

2. Monoclonal antibodies. Antibodies are proteins that healthy immune cells, called B lymphocytes, generate in response to infection. Whether medicinal or native, these complex molecules circulate in the plasma component of the bloodstream. What matters to many patients is this: antibodies are given by infusion (intravenous, IV) or, rarely, by injection. Herceptin (trastuzumab) is a good example of a targeted, monoclonal antibody treatment for breast cancer.

3. Hormonal treatments. These, for the most part, target estrogen receptors in breast cancer. (I am not convinced that these are truly “targeted therapies,” but as the NCI website lists these as such, I’ll go with the flow. Femara (letrozole), a drug that reduces estrogen and other steroid levels, falls in this class.

In a forthcoming post I’ll review the small molecule-type targeted therapies for cancer that have been approved by the FDA. After that, the monoclonals. If I’m feeling brave, I may cover hormonal treatments for breast and prostate cancer.

As for traveling in New Orleans, I hope to get back there soon enough. If I do take a cab there, I wonder what news the driver will report.

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The High Cost of Food-Borne Illness, and Some Steps To Avoid These in Your Home

A new report from the “Make our Food Safe” project, based at Georgetown University, makes clear that food-borne illnesses – from bacteria, parasites and a few viruses – are ever-present and costly.

The study, authored by Robert Scharff and funded by the Pew Charitable Trusts, finds that food-borne illnesses tally nearly $152 billion per year. This measure includes some subjectively-measured expenses like pain, suffering and missed work. Even without those, the toll registers above $100 billion – a huge sum, either way.

The main culprits are familiar: salmonella, that commonly reside in uncooked poultry and eggs, sometimes lace vegetables and lately tinge peanut butter, causes some 1.5 million illnesses per year. E coli 0157:H7, a dangerous bacterial strain that turns up disproportionately in ground beef and recently on fresh spinach leaves, is less prevalent but more often damaging; it takes kidneys and sometimes lives.

The Centers for Disease Control (CDC) provides a lot of useful information on its website regarding food safety.

As a doctor, and as a mom, I see this report as a nudge to be mindful in our kitchens, to follow what should be obvious advice from a collectively-conjured grandmother.

1. Before starting to prepare food, wash your hands with soap. Do this again after handling any raw meat, eggs or fish.

2. Keep raw meat, especially poultry, apart from any surfaces where cooked food is placed, stored or served. Cook chicken thoroughly, always.

3. The same goes for eggs.

4. Salad is one of the most dangerous foods we eat. It’s loaded with dirt from the ground. To wash lettuce for salad, let water pass over each leaf and rinse, fully, at least three times. Tomatoes should be handled similarly. Carefully peel carrots, cucumbers and most other vegetables if they’re to be eaten raw.

5. Unpeeled fruits like grapes and berries are handled like vegetables for salad; they’re washed at least three times.

(N.B.: this method of aggressively washing produce 3x is hardly full-proof; it reduces the amount of dirt on the surface of fruits and vegetables but does not completely eliminate germs.)

6. It’s hard, if not impossible, to adequately wash leeks, scallions, potatoes, mushrooms and most other vegetables. These are best washed and then cooked by sautéing, roasting, steaming or another method. The point is to cook with heat – of sufficient duration and intensity – to kill most bacteria, parasites and other germs.

7. Hygiene matters, especially around the kitchen and eating area. It’s a good idea to wipe down the table and kitchen counter surface after each meal.

These are just some suggestions for ways we can reduce the likelihood of being affected by food-borne illness at home. For people whose immune systems are compromised, such as those undergoing chemotherapy, with HIV and some other conditions, there’s reason to take extra care with salad and raw produce.

Knowing what we do about food-borne illnesses can influence choices we make when we eat outside of our homes. For example, in a restaurant, I’ll eat cooked but not raw spinach, because I know how difficult it is to properly wash that vegetable. If I order a burger, I’ll ask that it be very well-done, to minimize the risk from e. coli.

When traveling, I sometimes avoid uncooked fruits and vegetables entirely – but that’s another story.

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MedlinePlus, Now More Than Ever

Last week, ABC announced drastic cuts for its newsroom staff. The situation is similar at CBS, which in early February reduced its news-gathering personnel. These pull-backs by the major networks, paralleled by lessening or flat-out elimination of newspapers, will boost the number of people who check the Internet for medical news.

Two recent studies, from the Pew Center’s Internet & American Life Project and the CDC’s National Center for Health Statistics, confirm that most Americans are going on-line for health information. Compounding this effect, in all likelihood, are the uninsured, those reluctant to fork out hefty co-pays and some who are unable to dole out a deductible before they see a doctor.

Bottom line: the role of Internet-based health resources is likely to expand over the next decade. We need to know what’s out there –

We should start with MedlinePlus, a virtual superstore of free medical information. Co-sponsored by the National Library of Medicine (NLM) and the National Institutes of Health (NIH), this site is comprehensive and relatively clear of commercial bias. (There are significant exceptions, see below). It’s a useful origin for most any health-related search.

MedlinePlus covers more than 800 topics in English, 500 in Spanish and selective information in over 45 languages – you can read about anemia in Bosnian, hand hygiene in Creole or viral hepatitis in the Hmong language.

The site includes a medical dictionary, an encyclopedia (provided by A.D.A.M., a health education company that’s traded on the NASDAQ, ADAM), a compendium of drugs, supplements and herbs (put forth by the American Society of Health-System Pharmacists), a database on herbal remedies from Natural Standard, and some 165 interactive health tutorials.

There’s a direct link to the original on-line database that doctors used for decades, Medline/PubMed. This professional reference encompasses over 16 million articles published in more than 5000 scientific and medical journals. For the most part it’s a well-organized list of titles and abstracts, or summaries, of biomedical papers. A growing proportion of the articles are available in their entirety, and the abstracts can sometimes provide helpful clues in a medical search.

Another key connection is to ClinicalTrials.gov, an NIH-sponsored registry of all federally-sponsored and many privately-funded clinical trials conducted in the United States and elsewhere. For cancer patients, this database is crucial; previously, only doctors searching for clinical trials could access a public database of experimental treatments. (I’ll cover this site in a separate, future post.)

MedlinePlus offers an extensive catalogue of surgical procedure videos. You can watch an abdominal hysterectomy, vasectomy reversal or open heart surgery if you choose. While the films can be helpful, perhaps, to some patients who are deliberating about a procedure, some of my non-physician friends have found them rather bloody. I have some reservations about this component of the MedlinePlus site, in that many of the videos are provided by community medical centers and, the films are provided by a commercial enterprise, ORlive.

In recent years the number of visitors to MedlinePlus has hovered over 10 million per month. In 2009, the site received hits from approximately 128 million distinct Web addresses.

Last year, I spoke with Robert Logan, Ph.D., of the Office of Communications at the National Library of Medicine. “We’ve hit some sort of tipping point,” he said. “The internet has eclipsed other health information sources.”

Despite the comprehensiveness of MedlinePlus, there’s work to be done, said Logan. Some particular areas he hopes to improve on include ethics, epidemiology and statistics. “It’s hard for people to look at numbers and make clinical decisions,” he said. “But that’s a serious weakness in all areas of medicine all over the world.”

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Today’s Press on Targeted Therapy for Cancer

Today the NY Times printed the third part of Amy Harmon’s excellent feature on the ups and downs and promise of some clinical trials for cancer. The focus is on a new drug, PLX4032, some people with melanoma who chose to try this experimental agent, and the oncologists who prescribed it to them.

What I like about this story is that, besides offering some insight on the drug itself, it balances the patients’ and doctors’ perspectives; it explains why some people might elect to take a new medication in an early-stage clinical trial and why some physicians push for these protocols because they think it’s best for their patients.

And it provides a window into the world of academic medicine, where doctors’ collaborate among themselves and sometimes with corporations.

Here’s some of what I learned:

PLX4032 is a targeted therapy, a drug that’s designed to interfere with a specific, disease-causing molecular abnormality. It’s a small compound, taken by mouth, manufactured by Plexxikon that alters BRAF activity.

BRAF is a cellular enzyme, or kinase, that normally regulates how cells grow and divide. It’s encoded by an oncogene, a segment of DNA that can cause cancer when overly-expressed.

In most but not nearly all cases of melanoma, and in some other cancer clones, the malignant cells bear a mutated BRAF gene. This change can lead to a perpetually “turned on” state in the cells’ signaling machinery by which they proliferate without control. It’s thought that when PLX4032 works, it does so by blocking BRAF-mediated signaling and growth activity.

Harmon’s piece is long but easy to get through. She covers the human side of the story realistically. Some of the patients she describes with advanced tumors are desperate. The oncologists are, for the most part, hard-working idealists who work tirelessly for their patients.

There are real issues here, as in the setting of most clinical trials. I recommend this series to anyone who contemplates enrolling in a new drug study.

A remarkable point, as reported, is that the patients who ultimately succumbed to melanoma after a long period weren’t angry. As described, they didn’t feel “used” by their doctors or otherwise. Rather, they expressed appreciation. If these reported feelings are representative, that’s a testament to the quality of the care they received on study and, perhaps even more so, to effective communication between the patients and their physicians.

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New Boss on The Office is a Breast Cancer Survivor

Jo's mock-biography (NBC, The Office)

There’s a new survivor on TV and she means business.

In the latest episode of The Office, Kathy Bates walked into the Scranton branch of Dundler Mifflen and onto my living room TV screen as Jo Bennett, CEO of Sabre, a fictitious Tallahassee-based company. An assistant and two large canines accompany her as she meets the crew. She’s firm, graying and very much-in-charge.

When the camera gets her alone, in focus, here’s what she has to say:

“I’m Jolene Bennett, Jo for short.

I’m a breast cancer survivor, close personal friends with Nancy Pelosi, and Truman Capote and I slept with three of the same guys. When I was a little girl I was terrified to fly, and now I have my own pilot’s license.

I am CEO of Sabre International and I sell the best damn printers and all-in-one machines Korea can make.

Pleased to meet ya.”

(from The Office, Season 6, Episode 16, “A Manager and a Salesman”)

—–

Jo’s words are clear, delivered with eyes straight at you. It’s hard not to wonder what’s the significance of her being a breast cancer survivor, on the show and to her audience, and why she lists this alongside her other achievements in a highly-accomplished, fabricated life.

Kathy Bates is not the first actress to portray a woman who’s had breast cancer, and Jo Bennett is hardly the first TV character who’s had treatment. But this introduction seems like a perfect, even targeted strategy to revisit the topic:

What’s the significance of being a breast cancer survivor in 2010?

Maybe Jo’s a warrior, veteran-like, hardened after battle. Or perhaps wounded, deeply, now guarded by the dogs and a fierce resume.

Does she feel entitled? Bitter? Seek pity? Bates doesn’t play it in any of these ways, at least not in this first airing.

There’s no Misery here. Rather she appears large, strong, smiling broadly.

She has a mock-biography, Take a Good Look, I’d like to read. From the pseudo-Sabre website:

“A trailblazer in the world of electronic office equipment, Jolene Bennett serves as the President and Chief Executive Officer of the Sabre Corporation…Mrs. Bennett has received awards and recognitions, including being named one of Enterprising Women‘s Magazine 25 Most Influential Executives of 2007 and being named as a finalist for Tallahassian of the Year by the editors of Tallahassee Magazine in 2005.

Mrs. Bennett, a former Southern beauty queen, knows the importance of giving back. She has also received numerous awards for her philanthropic efforts with, among others, the Negro College Fund, The Florida Great Dane Rescue Society, and the American Breast Cancer Foundation. As a breast cancer survivor herself, Mrs. Bennett is especially passionate about helping other strong women beat cancer the way she did…

Jo’s company’s name is pointed. A sabre is a sword of sorts, usually curved, thick and sometimes lethal. My mind wanders to saber-toothed tigers, ferocious and extinct. And then, of course, to the Sabra, a native Israeli like a prickly pear – sharp on the outside, sweet beneath the rough skin.

I have no idea where The Office is headed with this theme, nearly ten years since Barbara Ehrenreich’s “Welcome to Cancerland” and roughly five since Elizabeth Edwards started her first chemo sessions.

I’m struck by how little talk there’s been of Jo’s mission since the episode’s debut. I’ve read dozens of blogs, TV reviews, there’s nothing. The Great Danes get mentioned, but not the breast cancer. Are we inured to the subject?

This isn’t about big Pink and ribbons. I’m talking about real patients who get tumors and need treatments. Some get depressed. Some die. Stuff happens.

As an oncologist, I saw women respond distinctly to their surgeries, radiation, chemotherapy and other treatments. Besides, the tumors vary in themselves – responding, sometimes lingering, killing too often. Some people need lots of medical care, others skate through.

There’s no right answer here, no one size fits all.

Regardless, I can’t wait to see the show’s next episode. Pam’s having a baby, life goes on.

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News on Aspirin After Breast Cancer

There’s some astonishing news on the breast cancer front.

A study published on-line this week in The Journal of Clinical Oncology (JCO) suggests that regular, low-dose aspirin use reduces the risk of recurrence and death from breast cancer among women who’ve had stage I, II or III (non-metastatic) disease.

This is a phenomenal report in three respects:

1. The dramatic results: among women who’ve had breast cancer, regular aspirin use is associated with a reduced risk of recurrence and death from cancer by more than half;

2. The relevance; these findings might affect millions of women living after breast cancer, today;

3. The cost: aspirin is widely available, without patent restriction. Aspirin costs around $5 for 100 tablets, several months’ supply.

About aspirin:

First, a concern that’s cited in the report:

Aspirin is an old and generally safe drug, available over the counter, that can be very dangerous in people with have bleeding problems or low platelets (blood clotting cells). Among women with breast cancer who are actively undergoing chemotherapy, radiation and some other treatments, aspirin use can exacerbate bleeding problems and may be inadvisable.

Anyone who considers taking aspirin should discuss, first, with their doctor if it’s OK.

The study participants reported taking aspirin (acetylsalicylic acid, or ASA in medical parlance) at varying doses and for a variety of reasons. More than a third of the breast cancer survivors used aspirin for heart disease. In that scenario, the typical dose is a baby aspirin (81 milligrams) on most days. Other women reported they took the drug for muscle and joint pains, backaches, headaches and other reasons.

About the study:

The work derives from the Nurses’ Health Study, a three-decades-and-going-strong observational analysis of health among over 238,000 registered nurses.

This particular analysis hones in on 4,164 of those nurses who had non-metastatic breast cancer (BC) found between 1976 and 2002. The investigators monitored these post-breast cancer patients with periodic questionnaires until the time of their death or 2006. It’s a large study, involving some 45,139 person-years.*

About the findings:

Figure 1. Aspirin Use and Relative Risk of Death from Breast Cancer

Aspirin Use, Relative Risk for Death from Breast Cancer

These graphs represent data from “Aspirin Intake and Survival After Breast Cancer,” JCO, Holmes, et al,  published on-line 2/16/10. The data are listed in Tables 2 and 3 of the paper, multivariate analysis, with 1.0 as the relative risk for women who had breast cancer and do not take aspirin (ASA).

Figure 2. Aspirin Use and Relative Risk of Breast Cancer Recurrence

Aspirin Use, Relative Risk of BC Recurrence.

Among BC survivors who reported taking aspirin between 2 and 5 days per week, the chances of dying from breast cancer were 29 percent relative to the baseline (no ASA) group and the odds of BC recurring, 40 percent. In other words,  aspirin use was associated with a 71 percent decline in deaths from breast cancer and a 60 percent drop in the recurrence rate for these women.

For those who ingested aspirin 6 or 7 days per week, the effects were similar: the death rate from cancer was 36 percent and the recurrence rate 57 percent, both significantly reduced in comparison to women who didn’t use aspirin. Among survivors who used 0-1 aspirin tablets per week, there was no measurable effect on either breast cancer recurrence or survival.

The results applied pretty much across the board – to premenopausal and post-menopausal women, to those with Stage I, II, and to a lesser extent, Stage III disease and to survivors with estrogen receptor positive (ER+) and negative (ER-) tumors.

The findings were not anticipated, according to the investigators, because earlier studies failed to show that aspirin prevents breast cancer from developing in the first place. What’s different here, they speculate, is that aspirin inhibits some inflammatory molecules, like prostaglandins or cyclooxygenases. The authors suggest these enzymes promote growth and metastatic spread of tumors that are already present.

Some details:

The study statistics are sound, with good (low) p-values for the aspirin-use trends, meaning that the likelihood of the observations being due to chance is extremely low. There are some limitations: first that the trial was not randomized, and second, that the reported use of aspirin was based on survey data provided by the nurses. But the size of the study, involving more than 4000 women who had breast cancer, the duration of analysis (over decades) and the not-slight differences in results between the treatment groups speak to the significance and potential implications.

—–

*In this analysis, person-years would be defined as the sum, for all women registered in the study, of the years for which they’ve been monitored. For example if 3 women were evaluated, each for 10 years, the study would include 30 person-years of data.

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You’re Sick and I’m Not, Too Bad

“The insurance market as it works today basically slices and dices the population. It says, well you people with medical conditions, over here, and you people without them, over here…

– Jonathan Cohn, Editor of The New Republic, speaking on The Brian Lehrer Show, February 16, 2010*

There’s a popular, partly true, sometimes useful and very dangerous notion that we can control our health. Maybe even fend off cancer.

I like the idea that we can make smart choices, eat sensible amounts of whole foods and not the wrong foods, exercise, not smoke, maintain balance (whatever that means in 2010) and in doing so, be responsible for our health. Check, plus.

It’s an attractive concept, really, that we can determine our medical circumstances by informed decisions and a vital lifestyle. It appeals to the well – that we’re OK, on the other side, doing something right.

There is order in the world. God exists. etc.

Very appealing. There’s utility in this outlook, besides. To the extent that we can influence our well-being and lessen the likelihood of some diseases, of course we can!  and should adjust our lack-of-dieting, drinking, smoking, arms firing, boxing and whatever else damaging it is that we do to ourselves.

I’m all for people adjusting their behavior and knowing they’re accountable for the consequences. And I’m not keen on a victim’s mentality for those who are ill.

So far so good –

Last summer former Whole Foods CEO John Mackey offered an unsympathetic op-ed in The Wall Street Journal on the subject of health care reform. He provides the “correct” i.e. unedited version in the CEO’s blog:

“Many promoters of health care reform believe that people have an intrinsic ethical right to health care… While all of us can empathize with those who are sick, how can we say that all people have any more of an intrinsic right to health care than they have an intrinsic right to food, clothing, owning their own homes, a car or a personal computer? …

“Rather than increase governmental spending and control, what we need to do is address the root causes of disease and poor health.  This begins with the realization that every American adult is responsible for their own health.  Unfortunately many of our health care problems are self-inflicted…

Now, here’s the rub. While all of us can empathize, not everyone does. And few citizens go to medical school. Some, uneducated or misinformed, might sincerely believe that illnesses are deserved.

So let’s set some facts straight on real illness and would-be uninsurable people like me:

Most people who are sick – with leukemia, diabetes, osteogenesis imperfecta, heart disease, multiple sclerosis, scoliosis, glycogen storage disease Type II, depression, Lou Gehrig’s disease, sickle cell anemia, rheumatoid arthritis or what have you – are not ill by choice. They didn’t make bad decisions or do anything worse, on average, than people who are healthy.

Rather, they became ill. Just like that.

The idea of an insurance pool is that when everyone in the community participates, whoever ends up with large medical expenses is covered, explained Jonathan Cohn. When contributions come in from all, including those who are healthy, funds are sufficient to provide for the sick among us.

As things stand, the insurance industry divides us into likely profitable and unprofitable segments. “So you know if you’re one of the people born with diabetes, you have cancer, you had an injury that requires lengthy rehabilitation, tough luck, you’re going to end up in that pool of unhealthy people,” Cohn said.

Insurance is no cure-all, to be sure. It won’t take away my cousin’s cancer or fix Bill Clinton’s heart. That would require research and better medicines.

Depriving insurance, or care, to those who need it most is inconceivable to a society as ours was intended. It’s uncivil.

*as heard on The Brian Lehrer Show 2/16/10: Rates on the Rise

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Health Care Costs, Communication and Informed Choices

For those of you who’ve been asleep for the past year: the health care costs conundrum remains unsolved. Our annual medical bills run in the neighborhood of $2.4 trillion and that number’s heading up. Reform, even in its watered-down, reddened form, has stalled.

Despite so much unending review of medical expenses – attributed variously to an unfit, aging population, expensive new cancer drugs, innovative procedures, insurance companies and big Pharma – there’s been surprisingly little consideration for patients’ preferences. What’s missing is a solid discussion of the type and extent of treatments people would want if they were sufficiently informed of their medical options and circumstances.

Maybe, if doctors would ask their adult patients how much care they really want, the price of health care would go down. That’s because many patients would choose less, at least in the way of technology, than their doctors prescribe. And more care.

What I’m talking about is the opposite of rationing. It’s about choosing.

Several recent stories have considered the problem of physicians not talking with their patients about treatment limits. Last month the journal Cancer published a study, based on canvassing over 4000 doctors who care for cancer patients in California, North Carolina, Iowa and Alabama, revealing that only a minority of physicians would raise the subject of a DNR order or hospice care for patients with metastatic cancer and a short life expectancy.

When it comes to recommending palliative care, aimed at patients’ nutrition and comfort, rather than cure, some doctors remain tight-lipped. Many good physicians, including cancer specialists, are reluctant to stop prescribing chemotherapy and aggressive treatments. The reasons vary. Based on my experience as a practicing oncologist, I’ll list a few:

Some doctors think it’s better for their patients if they are upbeat, and this may indeed be true. Conversely, many patients choose doctors who are optimistic: if you tell patients there are no treatment options, they’ll go elsewhere. Most patients, of course, do want treatment; more than a few are desperate enough to try anything a doctor says might work.

Another, unfortunate factor is financial pressure; giving treatment and doing procedures is far more lucrative than simple exam and discussion-based visits. I’m afraid, too, that many physicians don’t recognize the extent they’re influenced by effective marketing, usually blatant but sometimes subtle.

For others it’s an ego thing – doctors try to “outsmart” a disease, even when it’s not feasible, trying one therapy and the next, to no avail.

Harder to assess, still, is doctors’ internal unwillingness to give up on some patients because they care about them so much. Some excellent doctors may become so invested in a case that they, themselves, cannot be objective.

Besides, “throwing in the towel” is not something most good doctors like to do. And it’s not something most patients want to hear about.

Yet, maybe some dying patients would appreciate a doctor’s honesty –

These issues relate directly to the practice of oncology, the area of medicine I know best. But similar hesitations and conflicts of interest arise among doctors in most fields – cardiologists caring for people with severe heart disease, neurologists caring for people with end-stage Parkinson’s, and infectious disease experts caring for people with late-stage HIV, to name a few.

If doctors could somehow find the time, and take the trouble, to talk with their patients in a meaningful way, and then heed their patients’ wishes, they might find that many patients would, of their own volition, put a brake on health care spending.

For this reason, among the changes in health care I most favor is greater support for primary care and non-procedural services. If  were paid more for thinking and communicating, rather than ordering tests and performing treatments in a perfunctory manner, they and their patients might opt for less expensive, more humane remedies.

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On Precious

This is my first film review, if it is that.

I was tempted to write about Ethan Hawke, hematologist among vampires in Daybreakers, but gore’s not my favorite genre. A mainstream choice would have been Harrison Ford solving the enzyme deficiency of Pompe disease in Extraordinary Measures, but I didn’t get sucked in. I chose Precious, instead.

Poster for Precious, the film based on the novel “Push,” by Sapphire

This luminous movie relates to the practice of medicine everyday, big-time. Directed by Lee Daniels and based on the novel Push by Sapphire (Ramona Lofton), the film follows a very obese Harlem teenager who’s pregnant with a second child by her abusive father. She’s humiliated daily by her welfare-dependant mother who forces her to cook greasy food and perform sexual acts all-the-while telling her she’s worthless. She’s 17 years old and can’t read. Things can get worse, and do.

What’s relevant to medical lessons?

For doctors –

The message of Precious, that every human life has value, should be obvious to every person employed in the health care system. But I know too well that’s not true.

When I was a medical student in 1985, working with a team of surgery residents, we cared for an obese young woman from Harlem who came in with a life-threatening case of pancreatitis. Her internal insulin-manufacturing organ was so inflamed that her entire gigantic abdominal cavity was tender and bloody. During what seemed like an endless operation in the middle of the night I stood and held firmly a retractor as best I could. The next morning and thereafter, when we made rounds, the residents called her “the whale.”

I learned a lot about pancreatitis and surgery that month. But I couldn’t understand how she, my patient, tolerated the team’s attitude. She didn’t seem to mind, perhaps because we saved her life and the care we provided was free. In retrospect, I wonder if maybe, like Precious, she was too-accustomed to disrespect.

Of course, this is an extreme example from 25 years ago. And I know from my experience working for years in a hospital, and in my years as a patient, that most doctors treat most patients with appropriate dignity. But those residents I worked with then are senior practicing physicians now, likely some on the faculty of medical schools. The disposition to disparage patients, more often subtly – in keeping them waiting without good reason, in dismissing their long lists of real concerns, in somehow putting ourselves above them and even, still, occasionally expressing frank contempt for some unfortunate souls still permeates the hospital culture.

For patients –

When Precious is abused, her mind runs elsewhere. She imagines herself, huge body and all, cast glamorously among television stars or dancing with popular singers. She pretends that she’s all right even when she’s not, really. Finally she speaks up for herself, telling a social worker about her predicament.

Ultimately that’s what makes the difference – her confidence in the value of her own bruised life. She recognizes that, despite everything, she’s a full-fledged human deserving better and has the guts to ask for help. By insisting, by knowing, that her life matters, she pushes herself out, if only partly, from the bleakest of circumstances.

If you’re disabled, hurt, wounded, damaged – ask for help when you need it. Respect yourself, as Precious did. That sends a signal to doctors that you value your life, and they should treat you accordingly.

Hopefully they’ll be paying attention.

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Henrietta’s Cells Speak

“One of the ways that I gained the trust of the family is that I gave them information.”

(R. Skloot, a journalist, speaking about her interactions with Henrietta Lacks’ family, Columbia University, Feb 2, 2010)

This week I had the opportunity to hear a terrific talk by Rebecca Skloot, author of a new, flying-off-the-shelves book –The Immortal Life of Henrietta Lacks.

Mrs. Henrietta Lacks died of metastatic cervical cancer in the colored ward at Johns Hopkins Hospital in Baltimore, MD in September 1951. She lived no more than 31 years and left behind a husband, five children and an infinite supply of self-replicating cancer cells for research scientists to study in years to come.

HeLa cells with fluorescent nuclear stain (Wikimedia Commons)

Like many doctors, I first encountered HeLa cells in a research laboratory. Investigators use these famous cells to study how cancer cells grow, divide and respond to treatments. I learned about Mrs. Lacks, patient and mother, just the other day.

Skloot chronicles her short life in fascinating detail. She contrasts the long-lasting fate and productivity of her cells with that of the woman who bore them. She connects those, and her human descendants’ unfortunate financial disposition, to current controversies in bioethics.

In the years following their mother’s death, scientists repeatedly approached her husband and asked her young children for blood samples to check the genetic material, to see if their DNA matched that of cell batches, or clones, growing in research labs.

The issue is this: her husband had but a third-grade education. The children didn’t know what is a “cell,” “HLA-testing” or “clone.”

The family had essentially no idea what the doctors who’d taken, manipulated and cloned their mothers’ cells were talking about, Skloot recounts. They thought the doctors were testing them for cancer.

Years later, when they learned that their mother’s cells were bought, sold and used at research institutions throughout the world, they became angry and distrustful. The problem was essentially one of poor communication, she considered.

“Even a basic education in science would have helped,” Skloot said. “Patients, they want to be asked, and they want to be told what’s going on.”

Well said!

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Are Doctors Necessary?

Ten years ago, my colleagues and I squirmed in our swivel chairs when a few tech-savvy patients filed in bearing reams of articles they’d discovered, downloaded and printed for our perusal. Some of us accepted these informational “gifts” warily, half-curious about what was out there and half-loathing the prospect of more reading. Quite a few complained about the changing informational dynamic between patients and their physicians, threatened by a perceived and perhaps real loss of control.

How a decade can make a difference.

In 2000 the Pew Charitable Trusts initiated the “Internet & American Life Project” to explore how the Web affects families and communities in matters of daily life. Susannah Fox is an associate director of the Research Center project.

“It’s the ultimate information appliance” she says of the Internet. Now that it’s in most people’s homes, people use it as they choose.

And that’s quite often –

In 2008 over 140 million Americans, a majority of U.S. adults, looked for health information on-line, according to the Center’s 2009 report. Nearly 60 percent of those admit that a recent Internet search influenced a medical decision.

“Back in 2000, our data was used to prove the concept that people were going on-line to get heath care information,” she says. But that’s no longer the issue.

“With Facebook, MySpace and Twitter, there’s a new frontier” she states. “I think we’re at a new inflection point, and now is the time to have a very clear conversation on health care.

There’s been a significant shift on the physicians’ side, too.

“It’s become clear that increased communication and discussion can change care in a positive way” says Dr. Barron Lerner, a primary care physician and medical historian at Columbia University. His most recent book, When Illness Goes Public: Celebrity Patients and How We Look at Medicine, considers how ailments in the public realm can influence peoples’ perception of illness and inform their care choices.

“The Internet can be amazingly good to get people up and running” he considers. Lerner encourages his patients who have cancer to visit the National Cancer Institute (NCI) website.

“Why not go on, and explore,” he tells them. “Now as for how much they can absorb there, I don’t know,” he adds. “It’s a very hard website.”

Dr. Gretchen Berland is a primary care physician, videographer and former MacArthur Foundation fellow at the Yale University School of Medicine. She led an early study on the quality and accessibility of web-based medical information in that was published in the Journal of the American Medical Association in 2001.

“The Internet gives people a sense of control,” she says. “People use the Web to augment the information they’re given by their physicians, to look for a second opinion, and to search for clinical trials.”

But despite the wealth of information, and good quality of many sites, Berland sees limits in the Internet’s use, particularly for patients with complex, serious conditions like cancer. Even if online materials are comprehensive and accurate, they rely on people’s ability to find and understand them.

The Internet is not enough to help most people, she states.

Recently Berland searched on-line resources on behalf of a friend who had cancer surgery. When she looked at all the data, including material gleaned from some physician-oriented sites, there were gaps. “It wasn’t clear what he should do, despite how much information is out there.”

That’s the paradox of the Internet, she notes. “It’s hard to know what applies to a particular person’s unique and complex medical circumstances.

“One thing the Web doesn’t do is personalize the information,” she says. “That’s what physicians do.”

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A Note on Blogging and Medicine

Some of you may have noticed I’ve been quiet for a few days. That’s because I’ve been working on the elements of my new Medical Lessons site. Among the things I’ve learned since starting this project in mid-November, just 2.5 months ago, is this –

Blogging is like practicing medicine in some surprising ways:

1. You learn how to blog by doing it;

2. What you say, and how you say it, makes all the difference;

3. Some people will appreciate your style, others won’t;

4. You have to be careful, details can make things go right or wrong;

5. There’s never enough time in the day;

6. It’s fun, interesting and rewarding (largely in intangible ways);

7. You have to stay current to be good at it;

8. You get to interact with all sorts of people;

9. You’re constantly learning;

10. I love it.

As soon as the new site is ready, you’ll find the directions automatically.

Not to worry – I’ll be writing lots, then and there. Once the formatting’s done I’ll have more time to spend on ideas and information.

See you there!

ES

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A Visit With My Oncologist

Today I visited my oncologist for a checkup.

Waiting to see her, I sat in a floral fabric chair by a matching wood veneer coffee table strewn with worn magazines – Architectural Digest, Better Homes and Gardens and some old Time issues – I couldn’t help but think of how I was feeling seven years ago.

Then I was anxiously waiting to know my blood counts – the white cells, red cells and platelets – to see if they were sufficient for my scheduled chemotherapy.

That January, my white blood cells were so low that some doctors thought I should enter the hospital for IV antibiotics. (I declined.) My mouth was so full of sores I could hardly speak or eat. My hair was gone and I wore a strange wig. My right arm was broken (yes, I’m right-handed) so I couldn’t write or type. I was pale, weak with anemia and covered with bruises.

Chemo-brain, which I’d never learned about in med school, was just starting to set in. Before then, I’d always taken pride in keeping up with medical and science journals. But I could barely muster the energy to take a glance at those heavyweights. Even regular magazines appeared fuzzy, a scary symptom for an oncologist who knows too well that breast cancer cells can spread upstairs.

I wanted my next treatment. I wanted to get it over with, to put the breast cancer behind me.

After a while my oncologist stepped out into the waiting area and guided me to the hall by her office. “The cells are low,” she said. “We’ll have to wait another week, that’s all.”

I knew she was right. But a week seemed like a lifetime to me then.

I understood that giving chemotherapy suppresses the bone marrow, the body cavity where blood cells form. If my white cells dropped any lower, I’d be at serious risk for bacteria in the blood or invasive yeast in my mouth and throat. If the treatment reduced the red cell-forming elements in the marrow, I’d become more anemic. Already I was on a medication that affected the function of platelets, the blood-clotting cells. If the platelets fell further, I’d be at greater risk for bleeding.

I had no choice but to wait. So I did. The next week I got my treatment, and we were back on track, at least for a while.

Today, sitting in a similar chair, I calmly read the arts section of the newspaper and started working on the crossword. I’d tucked the New England Journal of Medicine into my bag, thinking I should read that, but it didn’t seem right. I wanted to remember what it’s like to be a patient who doesn’t know if she’ll make it through.

Several of my friends, mainly women, are affected now by cancer that’s spread. They go to see their oncologists regularly, and sit and wait for their blood counts, and sometimes get their treatments. Most hold undeniably upbeat, positive attitudes. But the reality is tough-going, day-to-day and month after month, with no easy end in sight.

How much easier it is to look back on a situation – a tumor – that was removed in an early stage. My cancer treatment wasn’t easy, but I don’t regret it for a second.

When my oncologist took me into her office today we chatted for a while and then she examined me.

“Come back next year,” she said.

In my medical storybook, it doesn’t get much better than that.

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How to Avoid Death in the ICU

Something I learned as a medical intern is that there are worse things than dying.

As I recall, it was sometime in April, 1988. I was putting a line in an old man with end-stage kidney disease, cancer (maybe), heart failure, bacteria in his blood and no consciousness. Prince was on the radio, loud, by his bedside. If you could call it that – the uncomfortable, curtained compartment didn’t seem like a good place for resting.

An attending physician, a smart guy I respected, approached me as I completed the procedure.

“It’s kind of like Dante’s seventh circle,” he noted.

Indeed. A clear, flexible tube drained greenish fluid from the man’s stomach through his nose. Gauze covered his eyes, just partially. His head, hands and feet swelled with fluid. A semi-opaque hard-plastic instrument linked the man’s trachea, through his paper-taped mouth, to a noisy breathing machine. His skin, barely covered by a stained hospital gown, was pale but blotchy from bleeding beneath. An arterial catheter inserted by his wrist, just where I might have taken his pulse had he been healthier. A fresh adhesive covered the cotton gauze and brownish anti-bacterial solution I’d placed over his lower right neck.

“Yeah,” I said as we walked out of the room to review another patient’s chart.

I wondered if the ICU staff would mind my changing the radio station, just in case the patient could hear but not tell us he preferred WQXR.

“There’s no way I would let this happen to me,” I remember thinking.

—–

This month, a report in the ACS journal Cancer indicates that most U.S. physicians don’t talk with their patients about end-of-life issues until death is imminent, if they do so at all.

The study, based on canvassing over 4000 doctors who care for cancer patients in California, North Carolina, Iowa and Alabama revealed that only a minority of physicians would raise the subject of a DNR (do not resuscitate) order or the possibility of hospice care for a patient with metastatic cancer with a life expectancy of 4-6 months. The article has generated considerable, appropriate attention in the press and for good reason – it bears on health care costs, patients’ rights, doctors’ communication and time constraints and a host of points relevant to the practice of medicine in 2010.

For purposes of this post, today, what I’ll say is this much:

Don’t wait for your doctor to talk to you about death and dying. Be proactive about your wishes and the kind of care you wish to receive, especially if you’re sick with a serious medical condition. Take the initiative – document your end-of-life preferences as best you can, according to the law of your state, and tell your physicians about any limits you’d like to set on the care you might receive.

It’s a conversation worth having, early.

——-

Here’s a very-partial list of resources for people who’d like to learn more about advance directives, living wills, DNR orders, hospice care and other end-of-life concerns:

MedlinePlus on Advanced Directives;

New York State: information on Health Care Proxy forms and DNR orders

Family Caregiver Alliance on End-of-Life Choices

Hastings Center on End of Life Issues

American Hospice Foundation

Cisely Saunders Foundation

Hospice Foundation of America

The National Hospice and Palliative Care Organization

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Blood Matters

January, the coldest season in my vicinity, turns out to be National Blood Donor Month. This designation, a legacy of the Nixon administration (see Proclamation 3952 of December 31, 1969), I learned last week.

Besides, blood’s hot.

HBO’s True Blood received an invigorating, early renewal notice last summer; a third season will come out in June. And on film 2009 witnessed a quick, hungry revisit from Twilight, among others vampire flicks. Just this month, Ethan Hawke revealed himself in Daybreakers as Hollywood’s first hematologist-protagonist.

So it seems that now’s the perfect time to talk about it –

Blood, always my favorite Aristotelian humor, comprises two elements – plasma (a hazy yellowish fluid) and cells. The plasma bathes the blood cells in a mixture of salts and proteins as they travel within the walls of blood vessels throughout the body (the circulation) and in the chambers of the heart. Plasma proteins include some hormones, enzymes, clotting factors and antibodies.

Let’s start with some basics on the cellular components of blood: white blood cells, red blood cells and platelets:

neutrophil as seen in a peripheral blood smear, Wikimedia Commons (WC)

White Blood Cells

White blood cells (WBCs), physically larger than the rest, serve as warriors against infection. These include a cast of various types, each with a distinct role in battling germs. The most familiar white cells in the “peripheral blood” – as doctors refer to fluid passing through arteries and veins – are neutrophils, lymphocytes and monocytes. Two other forms, eosinophils and basophils, emerge from the bone marrow and typically travel in lesser numbers.

scanning micrograph, red blood cells, WC, adapted NIH image

Red Blood Cells

Red blood cells (RBCs), the most abundant and usually uniform blood cells, carry and deliver oxygen throughout the body. Mature, circulating red cells are disc-like in shape, indented on each side, and lack nuclei. They’re loaded with hemoglobin, a complex, iron-laden molecule that binds oxygen and turns blood red.

When someone receives a transfusion, that’s usually a unit of packed red blood cells, concentrated red cells from which most of the donor’s white cells, platelets and plasma have been removed.

Platelets

Platelets are tiny, blood clotting cells. Like red cells, these cells circulate without nuclei, but they’re irregular in shape and sticky, loaded inside with plug-forming proteins and on their surfaces with adhesive receptors, ready to clump at the nick of a chin or a pinprick.

—–

Both cancer and its treatments can affect the bone marrow, where blood cells are formed. Some tumors, like leukemia and lymphoma, arise from blood cells. Other medical conditions cause blood cell problems, too. For example, chronic kidney disease causes anemia, and HIV infection leads to reduced T-lymphocyte counts.

For all these reasons, I think it’s helpful for everyone to have some understanding of blood and blood cells – any discussion of stem cells, bone marrow and transplantation presupposes some knowledge of these basics.

More to follow!

Meanwhile, if you’re searching for more blood info on the Web, I suggest these sites:

American Society of Hematology – Blood: the Vital Connection

America’s Blood Centers – What is Blood?

American Society of Clinical Oncology (Cancer.Net) – Understanding Blood Test Results

MedlinePlus – Blood and Blood Disorders

National Heart Lung and Blood Institute – Blood Diseases and Resources Information

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Why Give Blood?

Giving blood is something that’s close to my heart.

When I was 14 years old, I received seven units of packed red blood cells from strangers during and after spinal surgery. In 2003 when an orthopedist bravely cut the steel rod fused to my spine, readjusted it and inserted new hardware, I got another four units. So I’m keenly aware of this mitzvah, of giving blood. It saves lives.

Today, thousands will donate blood to honor the birthday of Dr. Martin Luther King, Jr.

As a practicing hematologist through 2006, I wasn’t aware of this phenomenon. Over the past week, I’ve scoured blood journals, blood-banking websites and even contacted a few leaders in the field, but found few doctors familiar with the tradition or what’s at least a trend as tracked by the all-knowing Source:

Google search Timeline view (1-16-10)

—–

It’s not clear exactly when this practice, now seemingly integrated with nationwide MLK National Day of Service events, began. The Orlando Sentinel published an article linking blood donation with MLK on January 14 1988:

Florida Blood Services campaign image January 2010

Donors giving blood from 2 to 7 p.m. Monday at the American Red Cross center, 341 White St., Daytona Beach, will be donating in memory of Dr. Martin Luther King Jr.

Each person will sign a scroll saying they donated blood in King’s memory. That document will be presented to Bethune-Cookman College during a special assembly Wednesday, said JoAnn Lord, Red Cross spokesman.

In response to a similar blood drive, Coretta Scott King wrote: ”The national holiday is a time for personal recommittment to do something — to reach out to your brothers and sisters in the spirit of our common humanity. Certainly the giving of blood so that others may live is a very important way of committing yourself to others.”

Today I spoke with Daniel J. Eberts, corporate communications manager for the Florida Blood Services.  Dan’s been working with that agency for over 22 years. “The goal is to create awareness of the ongoing need for blood,” he says. The agency collects blood every day of the year except for Thanksgiving and Christmas, he notes.

“Dan the Bloodman” – as Eberts is sometimes called – is not shy in his passion for blood donation. Rather, he’s on YouTube, singing on how you, too, can give blood.

On recent MLK Days the Florida agency has collected between 500 and 700 pints of blood, he reports. The holiday presents a special opportunity to gather additional, much-needed minority registrants for the National Marrow Donor Registry.

Eberts emphasizes how easy it’s become to sign on as a potential donor. “All you need is some cheek swabs,” he says. “There’s no blood sample required. Now, most of the hassle is with the paperwork.”

——

Here are some resources for people who’d like to know more about giving blood:

The American Red Cross provides information on when and where to donate blood, as well as helpful instruction on the process of giving for first-time donors.

The AABB, formerly the American Association of Blood Banks, covers transfusions and related therapies.

America’s Blood Centers – a large network of non-profit community blood centers.

The New York Blood Center – a terrific local resource for my neighbors, a pioneer in blood banking and resources for patients worldwide.

For those who’d consider bone marrow donation:

The National Marrow Donor Program helps patients with leukemia and other conditions find matching bone marrow donors.  The agency provides, also, financial assistance to some who can’t afford needed transplants.

—–

January is National Blood Donor Month. For those who can give, it’s never too late – the need is year-round.

And a personal note of thanks, from me!

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Beware the Power of Data Handling in Politics (and Medicine)

Into my Google Reader this morning came a post from Biophemera (an intriguing blog at the interface of art and science). Scientist-artist-blogger Jessica Palmer offers a provocative clip featuring Alex Lundry, a self-described conservative political pollster, data-miner and data visualizer.

Alex Lundry Chart Wars: The Political Power of Data Visualization
more about “Alex Lundry Chart Wars: The Political…

Some excerpts:

“These charts are meant to illustrate the political power of data visualization. It’s a discipline that’s only just beginning to bloom as a messaging vehicle…

“So what changed, why now?” he asks rhetorically.

“Well of course the internet…What’s really changed is data. We capture more data, we store more data and more data is available to us in machine-readable parsable format. So it’s really gotten to the point where anybody with a computer can create a data visualization easily enough…

“Here are a few quick lessons in graphical literacy…You’ll see that messing around with the origin and axis can make unimpressive growth look pretty amazing, right?…

——

Scary stuff. We’re vulnerable to brainwashing by pie graphs with pretty colors. Men are hired to collect and represent data with a particular aim. And there’s more to come this way, faster than ever by twitter.

So why here? Why a Medical Lesson?

Because the same is true for health information.

——

One of the first rules of medicine is knowing your sources. Before you make a decision, consider: did you read or hear about a treatment in a textbook, in a reputable journal, at a scientific meeting or over lunch with a representative from a pharmaceutical company?

Immersed in data as we are, it’s tempting to grasp at the best-presented material regardless of its intrinsic value. Nifty graphs can persuade or fool even the best of us.

For patients:

1. Know your doctor – be aware of industry ties, academic connections and other sources of pressure to perceive or publish results more clearly than they are;

2. Distinguish ads from articles about health – the difference is not always clear, especially on-line;

3. Read the fine print and identify the perspective of who’s depicting “data” in charts and graphs – when medical information comes onto your TV screen or magazine page, there’s a good chance someone’s got something to sell you.

For doctors:

1. Remember the difference between peer-reviewed journals and PeerView Press (a CME company with a host of industry sponsors, one of many such that provide free, neatly-packaged information targeted to busy doctors);

2. Take the trouble to read the methods and statistical sections of published papers in your field – your patients are counting on you to discern good studies from bad;

3. Don’t forget we’re human, too. We’re vulnerable, drawn to promising new results –

Mind those origins and axes!

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Moms Tweet About Blood and Cancer

This afternoon I found a Tweet from a colleague, a journalist who happens to be a mom in my community:

Tweet from SuSaw:

“RT @JenSinger: Hey, baby. What’s your blood type? Nothing against the Big Pink Machine… http://ow.ly/URkg

As a trained hematologist (blood doc), oncologist and breast cancer survivor, I couldn’t resist checking this out. Here’s what I discovered:

The link traces to MommaSaid.net. Turns out MammaBlogger Jen Singer counts herself among lymphoma survivors in remission. Another mom in remission, I might add –

Jen clues us in on a new breast cancer awareness campaign that migrated to Facebook but three days ago – breast cancer awareness ? I updated my Status with my Bra colour ? and, as of this moment, has over 57,000 fans. Her solidarity with breast cancer patients and their loved ones is very real. She’s at increased risk, among other reasons for her sensitivity to the issue.

Jen plugs for greater public consciousness of other malignancies including tumors that arise from blood cells – conditions like non-Hodgkin’s lymphoma, leukemia and myeloma. She’s particularly concerned about a young neighbor, a teenager with recurrent leukemia, who needs blood now.

In a post “O Positive is the New Pink” she writes:

“So, I ask you this: Please put your blood type in your Facebook status and ask your friends to do so, too, to raise awareness for lymphoma and leukemia. Mine is O+, a blood type…

I was blown away by this, and impressed. What social media might do for the practice of hematology!

With just a few clicks at the keyboard and some thousands of on-line connections, one lymphoma survivor has improved the chances that one girl with leukemia will get the platelets she needs. And, maybe thanks to the Facebook blood typing information campaign, more potential blood donors will connect with those who need cells in the future.

Last year, Phil Baumann listed 140 potential applications for Twitter in health care. I was curious but skeptical. Now I’m partly persuaded, at least.

Besides, just think what three moms can do. It takes a village…

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More soon – on giving blood, blood types and blood cells.

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