A Note on Positive Thinking

Today I came upon a Jan 24 op-ed, A Fighting Spirit Won’t Change Your Life by Richard Sloan, PhD, of Columbia University’s Psychiatry Department. Somehow I’d missed this worthwhile piece on the sometimes-trendy notion of mind-over-matter in healing and medicine.

Sloan opens with aftermath of the Tucson shootings:

…Representative Giffords’s husband describes her as a “fighter,” and no doubt she is one. Whether her recovery has anything to do with a fighting spirit, however, is another matter entirely.

He jumps quickly through a history of the mind cure movement in America: from Phineas Quimby‘s concept of illness as a product of mistaken beliefs – to William James and New Thought ideas – to Norman Vincent Peale’s 1952 Power of Positive Thinking – to more current takes on the matter. These ideas, while popular, are not reality-based.

In his words:

But there’s no evidence to back up the idea that an upbeat attitude can prevent any illness or help someone recover from one more readily. On the contrary, a recently completed study* of nearly 60,000 people in Finland and Sweden who were followed for almost 30 years found no significant association between personality traits and the likelihood of developing or surviving cancer. Cancer doesn’t care if we’re good or bad, virtuous or vicious, compassionate or inconsiderate. Neither does heart disease or AIDS or any other illness or injury.

*Am. J. Epidemiol. (2010) 172 (4): 377-385

The Times printed several letters in response, most of which point to pseudo-evidence on the matter. All the more reason to bolster public education in the U.S., people won’t be persuaded by charismatic, wishful thinking about health care.

It happens I’m a fan of Joan Didion’s. I was so taken by the Year of Magical Thinking, in fact, I read it twice. Irrational responses, and hope, are normal, human responses to illness, disappointment and personal loss. But they’re not science.

Keep it straight.


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An Oncologist Considers Rare Lymphomas in Women With Breast Implants

I have to admit that when I first read about the FDA’s report tying rare cases of anaplastic large cell lymphoma to breast implants, my mind raced with a strange blend of excitement, intense interest and concern. My thoughts shifted from “wow, that’s really interesting” to “exactly what did the FDA find” to “should I be worried?”

So I’ve decided to write this morning’s post from my perspective as an oncologist who spent roughly 15 years of her life studying the causes of lymphomas and related blood malignancies. Some readers of this blog, who fortunately at this point in ML’s slow-but-steady growth are mainly strangers, may be unaware that understanding rare lymphomas was what I lived for in my research work, which occupied the bulk of my time and thought, which I loved very much (as strange as that may seem to some) and which I miss intensely, still, today.

The reality, as very-carefully documented by the FDA in its excellent analysis (which, in my opinion, far surpasses that of most case series reported in the medical literature; I’d give the agency an A+ for detail, thoroughness, clarity and openness about the limitations of the findings thus far), is that these cases of ALCL are few and far between: a total of 60 cases, worldwide, as I reviewed in yesterday’s post. Sometimes just a few cases are indicative of a problem, and I think that is exactly what’s going on with these rare lymphomas.

The pathology is interesting: Essentially all of the ALCL cases are T-cell derived and express CD30. Anaplastic lymphoma kinase (ALK) was negative in each of 26 cases examined for that receptor. The findings are plausible in the context of an aberrant immune response – which can occasionally become malignant – to a foreign body or particular antigen associated with the implants. These oddly uniform characteristics among these rare lymphoma cases support that the FDA’s findings are not random.

Most of the ALCL tumors were limited to the area of the implant capsules, and could – as best I can tell from the few reports – be treated by removal of the implants and affected, adjacent breast tissue. These don’t appear to be aggressive lymphomas, as are some ALCL’s. I would go as far as to speculate that these might indeed be antigen-driven tumors; in this light, it would make sense in principle and in practice to treat these by removal of the implants, at least as a first-line approach.

So if I had a patient with this condition, I’d tell her that these lymphomas are very rare and, when they do arise, can usually be treated by removal of the implant. But I wouldn’t down-play the risk, which is tiny but real.

As an oncologist, I found most of the coverage of the FDA’s alert disappointing, the discussion dominated by plastic surgeons’ reassurances and device makers’ dismissals. Statements like “a woman is more likely to be struck by lightning than get this condition” – proffered by an Allergan spokeswoman as quoted and emphasized in the WSJ Health Blog, Bloomberg News, LA Times and elsewhere – are not helpful to women with implants who are genuinely concerned about their health.

Because I understand that once a woman has had one form of cancer, her risk of developing another tumor is elevated – from whatever genetic, environmental or other disposition she has for malignancy, and from treatment toxicity. Most of the women I’ve seen with implants after mastectomies have some problems considered minor – like thickening of the capsule and dimpling in peri-implant tissue. But these are the exact sort of abnormalities as described in the FDA’s alert, for which there is now a recommendation: evaluate and report cases to the FDA.

Ultimately this is an issue about informed consent – and I don’t mean by this the paperwork, but the reality of women with choosing, or not, to get breast implants. Doctors need more information about these rare lymphomas: how often these arise, why they occur, and how they should be managed so as to cause the least harm when and if treatment is necessary.

The FDA provides a helpful list of sources, from which I’ve selected those that seem most relevant (see reference page). Of historic interest, also, is a NEJM perspective from 15 years ago on the debate about rheumatologic illness, the public’s perception and risks associated with breast implants.


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FDA Reports on Association of Breast Implants and a Rare Form of Lymphoma

Yesterday the FDA issued an alert about a possible link between breast implants – saline or silicone – and a rare form of lymphoma called anaplastic large cell lymphoma (ALCL). These lymphoma cases are exceedingly rare, but the association appears to be significant.

The FDA identified a total of approximately 60 ALCL cases in association with implants, worldwide. Of these, 34 were identified by review of published medical literature from 1997 to May, 2010; the others were reported by implant manufacturers and other sources. The agency estimates the number of women worldwide with breast implants is between 5 and 10 million. These numbers translate to between 6 and 12 ALCL cases in the breast, per million women with breast implants, assessed over 13 years or so.

In women who don’t have implants, ALCL is an infrequent tumor, affecting approximately 1 in 500,000 women is the U.S. per year. This form of lymphoma – a malignancy of lymphocytes, a kind of white blood cell – can arise almost anywhere in the body. But ALCL cases arising in the breast are unusual. The FDA reports that roughly 3 in 100,000,000 women are diagnosed with ALCL in the breast per year in the U.S.

These are very small numbers. Still, the finding of ALCL tumors by the implant capsules is highly suggestive. Almost all of the implant-associated ALCL cases were T-cell type, whereas most breast lymphomas are of B-cell type. The lymphomas arose in women with both silicone and saline-type implants, and in women with implants placed for purposes or augmentation and for reconstruction after mastectomy.

The clinical features varied among the reported cases. From the FDA’s review:

… the median time from breast implant placement to ALCL diagnosis was 8 years, with a range from 1 year to 23 years. Most patients were diagnosed when they sought medical treatment for implant-related symptoms such as persistent seromas, capsular contractures, or peri-implant masses warranting breast implant revision operations. In each case, lymphoma cells were found in the effusion fluid (seroma) surrounding the implant, in the fibrous capsule, or within a peri-implant mass. Typically, there was no invasion beyond the fibrous capsule into the breast parenchyma.

Figure 1 illustrates the location of the reports of ALCL adjacent to the breast implant.

This illustration shows the breast implant placed under the skin and breast tissue. The implant is separated from the breast tissue by a fibrous scar capsule. ALCL lymphoma cells are shown in the effusion fluid between the breast implant and the capsule and attached to the capsule itself.

Figure 1. Presence of ALCL cells in close proximity to a breast implant. In most cases, the ALCL cells were found in the effusion fluid (seroma) surrounding the implant or contained within the fibrous capsule. ALCL is lymphoma, a type of cancer involving cells of the immune system. It is not cancer of the breast tissue, and typically, invasion of the lymphoma beyond the fibrous capsule into the breast parenchyma was not observed. Modified from Thompson et al, (2010).

With such a small number of cases worldwide, it’s hard to draw evidence-based conclusions regarding the appropriate treatment of these rare lymphomas. More from the FDA:

Treatment was reported for 20 patients. Most had the implants removed, and some went on to receive treatment with radiation and/or chemotherapy. Overall, the outcomes appeared to be more favorable than would typically be expected for systemic ALCL. Outcomes were reported for 19 cases. Of these, 14 patients had no evidence of disease at last follow-up. However, most cases were diagnosed with early stage disease, and follow-up on many cases was limited.

At this time, the FDA is advising health care providers to be aware of the possible diagnosis, to carefully evaluate breast implant patients with suspected ALCL, and to report all confirmed cases to the agency.

As for patients, the situation is troubling. The incidence of these tumors is quite low, almost immeasurable, and the prognosis – based on the few treatment reports – seems good. But many women do have some fluid, contractures, thickening and other complications around the implant capsules. Most of those physical aberrations surrounding the implants are not lymphoma.

It’s a Pandora’s box, but one that needs be opened. The problem is that if we biopsy every abnormality – such as a minor thickening or fluid accumulation adjacent to a breast implant – we’ll hike up the costs and, more importantly, the complications associated: With every needle stick there’s a risk of infection, additional scar formation and more. On the other hand, you wouldn’t want to overlook a treatable, early-stage lymphoma. Women need to know of the risks of implants, which can only be determined if doctors thoroughly investigate these sorts of complications.

The LA Times quotes Dr. Phil Haeck, president of the American Society of Plastic Surgeons: “I think there’s reason to be concerned about this, but there shouldn’t be reason for panic,” he said. According to that article: “Signs of ALCL associated with implants ‘are pretty dramatic. There’s a lot of swelling and pain. They won’t miss it,’ Haeck said.”

I’m not so sure. Lymphoma, including ALCL in my experience as an oncologist, can be very subtle.


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Another Brooklyn (and how I feel when I look in the mirror)

The image of Brooklyn Decker, a real woman and model from Middletown OH, streamed through my Google news feed this morning. I have to admire any person named Brooklyn, the place where I was born.

From a post on my BlogHer health RSS:

Brooklyn Decker on the cover of Sports Illustrated, in 2010

The BlogHer subject is Decker’s diet and exercise secrets: “…no matter how wealthy or famous you are, Decker says the only thing that really works is exercise, eating healthy and accepting your body for what it is that will make you succeed.”

Got it.

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Sad Stats for Science Knowledge in U.S. Schools

Today’s Times reports on our nation’s students’ poor science test results. The results are bleak: only 34% of fourth graders scored at a “proficient” level or higher; just 30% of eight graders scored at a proficient level or higher; 21% of twelfth graders scored at a proficient or higher level in science.

The mega-analysis, prepared by the National Center for Education Statistics, derives from 2009 testing of 156,500 fourth-graders and 151,100 eighth-graders, with state-by-state and nationwide metrics of those, and of 11,100 twelfth-graders. Student scores were ranked at one of three science knowledge levels for each peer group: advanced, proficient and basic, as defined by the Department of Education. Only a tiny fraction – as few as 1 or 2% of students – attained “advanced” scores on the science exams.

The complete report card analyzes the data by race, sex, urban vs. rural districts, private vs. public schools and other factors, and includes interactive state maps.

These numbers don’t bode well for our future-docs, or for empowered patients. With 70-80% of high school seniors lacking proficiency in science, informed consent and meaningful participation in health decisions are just theoretical concepts for most U.S. citizens.


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Why It’s a Good Idea to Get a Second Opinion, and Maybe a Third, But Rarely a Fourth

A few years ago I started writing a book on what it was like to be a cancer patient and an oncologist. This morning I came upon this section on second opinions:

Is it OK to get a second opinion?

Definitely. And there’s no need to be secretive about it, or to worry about hurting the doctor’s feelings. Second opinions are routine in fields like oncology, and are often covered by insurance. Be up-front: any decent oncologist can understand a cancer patient’s need to find a doctor who’s right for them, with whom they’re comfortable making important decisions. And in difficult cases, some specialists appreciate the chance to discuss the situation with another expert. So a second opinion can be beneficial to patients and physicians alike.

When things can get out of hand, though, is when patients start “doctor shopping.”  For example, I’ve cared for some patients with leukemia who’ve been to see over 10 oncologists. If you’re acutely sick, this sort of approach to illness can be counterproductive; it can delay needed therapy. From the physician’s perspective, it’s alienating; who wants to invest her time, intellectual effort and feelings for a patient who’s unlikely to follow up? Besides, oncology is the sort of field where each consulting doctor may have a distinct opinion. (If you see ten oncologists, you may get ten opinions…). Beyond a certain point, it may not help to get more input, but instead will cloud the issue.

As things stand, oncologists often discuss difficult cases with their colleagues. This happens at academic centers and hospitals, where tumor boards meet regularly to review the diagnosis and management of each cancer case, and informally in private practices, where physicians are likely to discuss certain aspects of treatment with their partners. For patients with very rare conditions, some oncologists will call experts in the field whom they may know through national meetings, journals, and other resources. What this means for patients is that through one consultant, they may be getting input of more than one expert, although they may not be aware.

So I recommend that patients with cancer, or any other serious or rare condition for that matter, get a second or third opinion about the best way to manage their illness. But at some point you’ve got to select one among those specialists, even if she’s not perfect, and stick with her at least for a while, until you have a good reason to switch or move on. Otherwise, you’re unlikely to have a doctor who cares when you’re really sick and, later, about your long-term well-being.


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The Broccoli Connection

(considering the Future of Health Care in America, and Life on TV in the Office)

This week’s NEJM is filled with good stuff.

There’s a super-extra-really important article on a new breast cancer drug, a PARP inhibitor called iniparib, for patients with triple negative breast cancer, and an accompanying editorial that matters. (Some ML readers might want to take a look at an article I wrote for Cure Magazine on new drugs, including PARP inhibitors, for treatment of metastatic breast cancer.)

There’s a perspective I still need to read on the scope of what nurses might do. Another on future nurses, and another on how to assess an ACO, which by the end of this health news-rich week every citizen should know stands for an Accountable Care Organization.

And there are some stomach-churning letters about the mammography screening debate.

But for this Friday morning, I’ll just mention the perspective piece called Can Congress Make You Buy Broccoli? And Why That’s a Hard Question. Really I think the better question is whether or not the government can force people to eat broccoli.

Michael waves a broccoli stalk in front of Kevin on the Office

And how could those NEJM authors have anticipated last night’s episode of the Office, that Michael would break HR rules by forcing Kevin to eat a stalk of raw broccoli, because he’d made a new year’s resolution to eat more vegetables? Kevin spat it out, forcefully and problematically for some viewers.

My tentative conclusion is that someone needs to teach Kevin and his colleagues how to cook.


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Cautious Optimism for a New Melanoma Treatment

This morning’s news feed delivered some seemingly excellent news for some people with melanoma. At least until now, this form of skin cancer has been considered incurable when metastatic. In the last year, we heard details about the ups and downs of ongoing clinical trials of new drugs to treat the disease.

The Times reports that Roche’s experimental drug prolongs life in patients with metastatic melanoma whose tumors have B-Raf mutations. The new findings, based on a randomized phase III, open-label and industry-sponsored trial, BRIM 3, were first communicated in a press release yesterday. The company indicates that the study met its primary endpoints: Patients taking the experimental pill, RG7204, lived longer, and went longer without disease progression, than those patients in the control arm who received standard chemotherapy (dacarbazine) injections every three weeks.

The new drug – a pill usually given at a dose of 960 milligrams twice daily – goes by several names:

RG7204 (Genentech is a Roche subsidiary)

PLX4032 (Plexxikon has a partnership with Roche to commercialize and develop PLX4032)

RO5185426 (as listed at ClinicalTrials.gov and the NCI thesaurus)

Since the Phase III study opened in January 2010, investigators recruited patients at numerous medical centers worldwide. According to the Roche press release, nearly subjects were randomized to receive either the experimental pill (960 mg) twice daily or dacarbazine (1000 mg/m2) by intravenous every 3 weeks. Patients continued on their assigned drug until the disease progressed or they experienced unacceptable toxicity. The most frequent severe adverse events were skin-related, including another, less-aggressive form of skin cancer, and mild, reversible liver abnormalities. The most common reported side effects were rash, joint pain, hair loss and fatigue.

What I can’t find are published details, such as by how long life was prolonged in patients receiving the experimental drug. The NIH Clinical Trials site indicates the investigators aim to recruit 680 patients, and the Times indicates that since the trial opened, 338 patients were assigned to the chemotherapy arm of the trial, while another 338 received the Roche drug.

According to Amy Harmon’s report in the Times:

About half of the 68,000 Americans who develop melanoma every year have a mutation in a gene, called B-RAF, that goes awry, for reasons not well understood, signaling cells to grow uncontrollably. The Roche drug works by blocking a malfunctioning protein the gene produces in cancer cells, but leaving the functioning proteins in noncancerous cells alone.

Roche, in its press release, indicates that: “based on these interim analysis results, patients on the control arm of the study will have the option to crossover to receive RG7204.” The results will be presented formally at a medical meeting this year. (Presumably that would be the annual ASCO gathering in June.)

I’m eager to see the findings, the extent and duration of remissions, degrees of toxicity, and more. This could be another good example of targeted therapy – giving a treatment that’s designed to block a known molecular defect in a tumor – that might dramatically alter the prognosis, and way of life, for some patients with malignant melanoma. But I am cautious in my enthusiasm, as the reports so far, and data interpretation, come from the company that sponsored the clinical trial and would sell the drug if approved.

(all links accessed 1/20/11)


addendum/clarification, Aug 2011: PLX-0432 was renamed vemurafenib.

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Regional Dialects on Twitter, and Other Things You Gotta Know

I was listening to All Things Considered yesterday while preparing dinner. A short, interesting story came on: You Have An Accent Even On Twitter. The NPR host, Robert Siegel, interviewed Jacob Eisenstein, a post-doc at Carnegie Mellon who has been examining regional variances in Twitter usage.

Some highlighted examples of Twitter dialecticisms:

In New York, people tend to do “suttin” (i.e. something, and usually having nothing to do with Sutton Place)

The use of “hella” to mean “very” as in “I’m hella tired” is more commonly iterated by people who’ve lived in Northern California.

(LOL is universally understood.)

I was sufficiently intrigued to track down Dr. Eisenstein’s paper, A Latent Variable Model for Geographical Lexical Variation, presented on January 8 at the annual meeting of the Linguistics Society of America in Pittsburgh. It’s a technical article befitting an MIT graduate, with un-trendy headings like “Cascading Topic Models,” “Inference” and heavy math. Still, I enjoyed the perusal.

Eisenstein and his colleagues started with a Gardenhose Twitter sample stream, which they say contained ~15% of public messages, from the first week of March, 2010. They whittled those down by selecting for tweets geo-tagged to the continental U.S. by authors who sent at least 20 messages during that period, and without URLs. Ultimately, they examined at some 380,000 Twitter messages (tweets) from 9,500 users.

The findings are really cool. (To be clear – that would be “coo” in Southern CA, or “koo” in Northern CA.)

Good to know that “af” signifies “as f-ck” (as in “very”), and is more commonly typed in Los Angeles than in some other parts. “Ima” for “I’m going to” is a New York kinda thing. “Gna” for “going to” is popular in Boston, but sounds familiar to this mother of a teenager in NYC.

From the Carnegie Mellon press release:

Studies of regional dialects traditionally have been based primarily on oral interviews, Eisenstein said, noting that written communication often is less reflective of regional influences because writing, even in blogs, tends to be formal and thus homogenized. But Twitter offers a new way of studying regional lexicon, he explained, because tweets are informal and conversational. Furthermore, people who tweet using mobile phones have the option of geotagging their messages with GPS coordinates.

…Automated analysis of Twitter message streams offers linguists an opportunity to watch regional dialects evolve in real time. “It will be interesting to see what happens. Will ‘suttin’ remain a word we see primarily in New York City, or will it spread?” Eisenstein asked.

I guess we’ll see how this progresses. I’m reminded of sometime around 8 years ago, when I tried cracking the IM code: “POS” meant “parent over shoulder.” That was easy. “Code 9” meant suttin similar, if I recall.


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Steve Jobs Takes a Medical Leave

The big health story of the week, headlining the business news, is that Steve Jobs, Apple’s founder and usual CEO, is taking another medical leave. This is hardly a surprising development, given that the 55 year old corporate leader has had a complex medical course since at least 2003. In August, 2004 he told Apple employees he’d undergone surgery for an islet cell tumor of the pancreas. He received a liver transplant, said Methodist University Hospital in Memphis in the spring of 2009. According to multiple reports, lately he’s been looking tired and gaunt.

There’s a lot to learn from this case without delving into the private details. First, about cancer pathology – that not all cancers of the pancreas (or any organ) are the same. The NCI estimates that approximately 43,000 people (roughly half men, half women) are found to have pancreatic cancer, and over 36,000 adults will die of the disease each year in the U.S.

Steve Jobs holding an iPhone in 2010 (Wiki Commons)

But Jobs’ case is special: he had a neuroendocrine tumor, a kind of malignancy that can arise from hormone-secreting islet cells in the pancreas. In general, neuroendocrine tumors cause symptoms from the hormones they secrete or from local effects; a slow-growing tumor lump can press on nearby nerves, vessels or ducts. Neuroendocrine tumors, which can be distinguished from other glandular tissues by special stains and molecular tests, usually confer a relatively good prognosis. According to the NCI, islet cell tumors of the pancreas are quite rare, with estimates of between 200 and 1000 new cases per year.

A liver transplant is definitely a complicated matter, with its own sets of long-term issues, needed medications to reduce the likelihood of graft rejection, and potential complications. By all reports Jobs is not interested in going public with specifics now. Still, there’s abundant speculation about his condition; when you hold a high office in a publicly-traded company, your well-being matters.

At another level, some people may simply care how he’s doing. Jobs is a creative, public person who’s delivered Pixar movies and iPods and Macs, and who’s been ill in recent years. Taking a medical leave, when you care about your work and you love what you do, and you’ve invested much of your life in that, is no easy decision. I hope he gets well and feels better soon.


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