Inkwell: Authors and Artists

    
Is the mortality rate for DCIS much higher than for prostate cancer?
  

    
David, a casual lit search suggests that this is kind of an impossible
question. 
  

    
Ok, then my original question may have additional answers.  My real
question is whether at least some of the reason has to do with the fact
that one set of tests is for women and the other set is for men, and
whether gender issues have anything to do with it.

We are not that many decades away from the doctors saying, "Your wife
is being admitted for a double mastectomy, but don't tell her until
it's all over."
  

    
i wonder if folks will look back at the epidemic of overly-aggressive
treatment of breast cancers as the equiv of the rush to give women
hysterectomies that was so common years ago.

and carole, thanx for validating my instinctive refusal of constant
mammograms. it just did not make sense to me to constantly expose tissue to
radiation
  

    
David, if anything, gender differences in surveillance and treatment
trend the opposite way. 

There are risks associated with routine mammograms, to be sure, but at
this point, 
  

    
[oops], I'm quite comfortable that the risks of skipping them are a
lot higher.
  

    
DCIS is a very odd diagnosis indeed.  When I was diagnosed about 15
years ago, the wisdom of the time was that:
  
There were carcinoma cells in the milk ducts, DCIS stands for ductal
carcinoma in situ as I recall, but by definition the rebel cells had
not formed tumors yet.  

They might form tumors (since I was young, they might form them fast,
and in young dense tissue I might not notice them while they were
small, but I was told I could just watch and wait if I wanted to defer
treatment.  I had been avoiding mammograms for reasons of radiation
until the diagnosis, but "just watching" in cooperation with the
oncologist at that time involved frequent mammograms, and was scary in
it's own way.) Sice it was extensive, when/if they did, there would
likely not be a clear margin for a lumpectomy.

DCIS is found in autopsies of many older women who die of other
causes, as Carole said, having caused no tumors or ill health, but the
variations of rate of growth was not then known, so that information
was hard to interpret.

The DCIS diagnosis  was called "stage zero cancer" since there was not
any actual tumor.  (But insurance company rate setters still interpret
that as a regular cancer diagnosis I am told.)

Since it was in all quadrants of the breast, and seemed to be
advancing according to the hard-to-read experimental MRI, in my case it
turned out that clear margins could not be possible without a full
mastectomy.

Since DCIS is stage zero, surgery without any radiation or chemo often
suffices to end the saga, and was suggested to me.  By that time --
having taken a full year to research, try other approaches, and think
it through, I saw that as lucky. Surgery only - and no lymph nodes
taken - such a deal.  

However, there is always the question of what if anything would have
happened without surgical treatment, even with my DCIS known to be
spreading. What a weird condition.


That was what one DCIS diagnosis was like, in the mid 1990s.
  

    
Hope that was not too much, uh, detail.  Meanwhile, an article about
which research to pay attention to:

"There’s error and there’s error. It’s one thing to be wrong about
low-impact treatments: to be wrong, for instance, about how much a
low-impact drug like aspirin or glucosamine helps modest knee pain in
athletes, or how much benefit you get from walking versus running, or
whether coffee makes your smarter or just makes you feel smarter. The
stakes run much higher when the treatments cost a lot in money or
health. Yet little in our regulatory, medical, or journalistic cultures
or practices acknowledges that."
 
<http://www.wired.com/wiredscience/20/10/10/how-to-set-the-bullshit-filter-when
-the-bullshit-is-thick/>
  

    
But here, we don't know whether the error would be in cutting out
mammograms -- because they really do save lives, we know that -- or in
continuing them, because of the radiation risk or other factors that
could cost some number of lives as well.

Ultimately, if Carole's main point is that people should be as well
informed as possible before making decisions, I'm all for that.

But there comes a point where there is information overload as well. 
I do not want to go back 30 years to the very real scenario I painted
above, but I also think that it isn't too much to ask that patients be
able to trust an expert in the field, maybe get a second opinion, and
then make a decision already so they can move on with their lives.
  

    
(If that is what they want, of course.  For some patients, reading
everything ever written on the subject before making decisions is
*exactly* the right choice.  But not for all.)
  

    
David, you wrote,

"I also think that it isn't too much to ask that patients be
able to trust an expert in the field, maybe get a second opinion, and
then make a decision already so they can move on with their lives."

Aw, it probably is NOT too much to ask.
In fact, for most people, that's exactly the way to go.  I envy folks
for whom things work that smoothly. 

But me -- if I'd followed that path  of "Listen to the doc, see one
expert, and get a second opinion"-- I'd've been dead three times over. 
  Because not every physician graduated in the top half of the class. 
And some experts are 'experts' only because they've had 12 additional
course hours. And some of those hours might've been CME's.

                                     
  

    
Gail, 

Great article !  Thank you!

<http://www.wired.com/wiredscience/2010/10/how-to-set-the-bullshit-filter-when-
the-bullshit-is-thick/>

    What the heck CAN you believe? 

No single research paper on any subject, that's f'sure. But at the
moment, since that research is all we've got, I'd rather read it than
ignore it.  

                              * * * 
A couple of years ago, we started collecting research that was , um,
less than well-done.  We meant it to be funny -- "Haha, look how dumb
the folks in THIS laboratory were" --  but it stopped being funny very
fast.  
  

    
Yup.  There is an incredible amount of bad science out there in
biomedical research.  A couple of decades ago, the history field was at
least somewhat chastened by a book called "Historians' Logical
Fallacies."  We badly need a "Biomedical Researchers' Logical
Fallacies."
  

    
Who was it who said that they had determined by a review of the
scientific literature that "research causes cancer in laboratory rats"?
  

    
 
Hi Carol, - an interesting discussion, I hadn't known about
Thermograms until this topic.

My question is how about testing these devices, the thermogram for
example, in clinical trials? I know something about clinical trials -
and let me explain what might be needed, below


And An aside, to #39, 
...research causes cancer in laboratory rats"..

 Don't know the answer to that, but maybe the same person who said if
you don't want to find any problems with <fill in the procedure> stop
looking at the data.

 And to the background for clinical trials.  
  
 As to the future for thermograms and testing in clinical trials, - if
all the promises from Obama's new health care legislation are kept -
then Thermograms, and many other devices, drugs etc. will get evaluated
in "Comparative Effectiveness Research" (or CER)

 It can be very complicated, and here's an example why. About a month
ago I spent several days at a research symposium with the Society of
Nuclear Medicine talking about Molecular imaging. (That's PET scans,
CT, MRI's etc).

 I'm a Pharmaceutical (drugs and devices) statistician and three  of
us were  there, with about 50 prominent M.D.'s,  to give advice on
issues of statistical methods, clinical trial designs, and so forth for
Molecular Imaging clinical trials.  We all understood  that was hard,
because basically there have been few or no clinical trials for
Molecular imaging devices. However, we were there because the future is
comparative evaluation of treatments, devices, procedures in Medical
care.

 And, the Obama plan has a "cost saving" component of CER for
determining which drugs/devices work so we can use them and which don't
work, and we stop using them and stop wasting money on them.

  The lessons from that symposium  are germane to thermograms.
Unlike prescription drugs, which must meet the "two adequate and well
controlled randomized clinical trials" standard to be approved, devices
(e.g. stents, MRI's, x-rays, etc.) need not meet that standard. There
is a different standard for devices.

  That's likely to change and there is a lot of press out there for
it.
e.g. this has an example of a platelet therapy that was apparently
never tested in clinical trials
http://www.jsonline.com/business/103800949.html


The huge dilemna it causes is, in the absence of randomized trials how
does one assess if one technology is better than any other?

 For molecular imaging, the problem is more complex because of the
stakeholders involved. 
 HOw could one do a "comparative study". 
The problem is challenging because first, there is the person who
takes/reads the scan (say an MRI or a thermogram). He sends that report
back to the doctor, possibly with a recommedation for treatment. The
doctor makes a decision as to how to treat. Now suppose one does find a
tumor and the doctor treats. 
 The challenge is, how or whether one can design a cliniical trial
that considers both decisions (the thermogram erader), the doctor who
treats, then, follows the patients for say 20 years to determine if the
woman lived longer, than -not- having that done. 

 The gold standard is to randomize, and how might that be done?

 Well one could consider randomizing women, one-half to have a
thermogram, the other half to an MRI, then to some particular treatment
based on what was found. Then follow for survival for 10-20 years.

 Gets pretty complex fast, and the studies take years, because they
involve survival.

As to whether or not, this is the future

http://www.minnesotamedicine.com/CurrentIssue/CommentaryPlotnikoffDec2009/tabi
d/3272/Default.aspx

http://tinyurl.com/2ea5bal


 The link spells out the consequences of Bad screening decisions

... The authors noted that “for every breast cancer death averted,
even in the age group for which screening is least controversial (ages
50 to 70 years), 838 women must undergo screening for six years,
generating thousands of screens, hundreds of biopsies, and many cancers
treated as if they were life-threatening when they are not.”....

IN the U.S. FDA is reconsidering the need for clinical trials for
devices

http://news.morningstar.com/articlenet/article.aspx?id=355465

.... We think it is unlikely that medical device companies will
conduct 10,000 patient trials on each product, and we believe going
forward we will have to rely more heavily on postmarketing registries
to track the performance of devices over the longer term...

 I think thermograms will get used, once they get tested and
demonstrated that they do save lives. 
  

    
Perhaps this technology will be developed further:

<http://gizmodo.com/5665071/what-is-this>
  

    
To #40
A valuable post, Chris.  Thanks for taking the time to put it
together. 

Comparing two procedures to identify the 'best' one might be an idea
whose time has come, but it does open some of those twisty little
passages of questions that lead only to more questions.  

 1.  Who determines which questions should be answered? 

(I mean, you'll get different answers to "Which machine identifies
early bc better?" and  "Which tells us sooner that something's going
wrong in that breast?"   "Sooner" is easier to answer than "better,"
because what does "better" mean, anyhow? Which machine sees bc more
often? more clearly? with fewer false positives? false negatives? less
patient pain? less expense?) 

2. Who's defining "breast cancer" ?  

In some circles , there's still a controversy about whether DCIS even
COUNTS as cancer.  And five pathologists are not necessarily going to
see one type of cancer in a given slide.  You're talking about a
discipline that's as much art as science. 

3.  FInally, maybe I missed something, but would you explain why
treatment is even part of the 'comparative' mix?  

You're talking about machines to help diagnose breast cancer.  Why,
then, is the pathologist's report not sufficient proof that the machine
did or did not identify cancer?  Isn't it enough to say "This machine
pointed to an abnormal breast-spot which, when biopsied, turned out to
be invasive lobular bc"?  What more can any machine offer? 
  

    
> Who's defining "breast cancer" ? 

I have always assumed that the reason DCIS is treated as cancer (for
the purposes of treatment) is that it DOES usualy turn into regular
cancer eventually -- and that one is more likely to develop cancer if
one has untreated DCIS than if one does not.

If it is true, as I have read, that DCIS usually progresses to
invasive cancer, then it seems as if discovering and treating DCIS at
an early stage will save you from the effects of treating invasive
cancer (chemotherapy, radiation, axillary dissection, lymphedema, etc.)
later on.

So then the tradeoff is between watchful waiting, with the possibility
of needing more radical treatment to avoid early mortality, or early
treatment with the possibility of having had surgery for a condition
that might not have progressed rapidly enough to matter.
  

    
I think it's fair to say that there is some art, and perhaps even
experientally-developed instinct (cf: deBecker and Gladwell), to the
discipline of pathology, but saying that pathology is "as much art as
science" is pushing beyond accuracy.
  

    
I'm not pushing thermograms, but--

Y'know who might benefit most from yearly thermograms?  Men and
late-teenaged boys with breast cancer.   

Male breast cancer is real, if uncommon. (In the US, about 200,000
women are diagnosed each year, in contrast with fewer than 2,000
men/year). 
 
They get mastectomies, just like women, and -- based on what I know
about female breast cancer and the use of mammograms for follow-up---
I'd guess that men are sent for mammograms too.    

If you guys have ever seen how a mammogram machine works, you'd
understand why I vote thermograms for males with breast cancer.  

* * * 

Speaking of male breasts, I don't know how often y'all get to see a
lot of young people, but I saw them all the time in New Orleans when I
lived there, especially at Carnival parades.  At any given parade, I'd
notice at least one, sometimes two or three pudgy pre-teen or
barely-teenaged boys with not-just-fat-chests, but with, well, small
breasts.  

I've since learned that, as these boys grow into their late teens,
some plastic surgeons have begun to do on them what would, in a woman,
be called a mastectomy.
 
I hadn't realized it might be a nationwide thing until I learnedd that
the same surgery is now being done on boys here in Asheville, too. 

I bring it up because I have some guesses as to the causes of breast
development in young males, and they tie in with Julie's question about
preventing breast cancer.  

First, though, let me ask if anybody else has noticed this phenomenon.
  

    
 Carole, thanks for #42 above. 

AS to diagnosis and treatment for cancer,  CER is to evaluate the long
term outcomes for people. In Breast cancer, it is in looking over the
long term outcomes that decisions are made whether all women should get
a mammogram or only some woman. And those decisions include whether
women may, by "false negative" or "false positive" get treated when
they don't need it or, don't get treated when they do need it.  The
outcome that matters, later, is whether they live or die.

 Thats' really the ultimate test. (I"m not suggesting that every
device or drug will be evaluated based on survival, cancer nearly
always kills, or kills sooner than not having cancer, so how long you
live after a diagnosis is very important)
 
 It  took a long time to get cancer treatments evaluated in clinical
trials. There was a time, when doctors would refer say, to the last 50
patients they treated, to judge whether a treatment worked or not.  The
notion of comparing one treatment to another, with randomization was
new, similarly for devices. For many devices, which may differ in small
ways from a predecessor (e.g. this new device has a titanium screw
instead of stainless steel) there has been no requirement to send those
to randomized trials. That may change.


 As to who determines, it happens all the time in cancer. For cancer
(I spend a lot of my time in cancer clinical trials), its the National
Cancer Institute, and, many times the Pharma companies who are doing
research into new treatments.


... Why,
then, is the pathologist's report not sufficient proof that the
machine
did or did not identify cancer?...

 Yes, it matters whether the machine did or didn't and it matters what
happens next, especially to those who were false positive or negative.
And whether the machine correctly determined the cancer and as well
the pathologist reading the machine output. Pathologists have their own
sensitivity and specificity. From time to time studies are done, say,
sending the same pathology slide to, say, 6 different pathologists for
a diagnosis and checking their "agreement".  Not surprisingly,
pathologists can disagree.


And for the machines, even with a high sensitivity and specificity
(which will never be 100%), there are people who will be treated, who
shouldn't have been treated (the machine said "cancer" when it was
benign), and people not treated when they should have.

  Multiply up to tens or hundreds of thousands  of people being
screened, diagnosed, and treated and it adds up.




 
  

    
#44:

Divinea,

You wrote:
"
I think it's fair to say that there is some art, and perhaps even
experientally-developed instinct (cf: deBecker and Gladwell), to the
discipline of pathology, but saying that pathology is "as much art as
science" is pushing beyond accuracy.
"

Thanks for putting it so delicately.  (grin) 

Nevertheless, though I'd consider amending the statement to "ALMOST as
much art as it is science," I'll stand by what I said. 
 
The UNamended statement came straight from a pathologist who teaches
pathology at a medical school, with the bulk of his students being
pathology residents.  

He encouraged me to get a THIRD path opinion after the first two were
so different that I thought my slides had gotten mixed up with someone
else's.    
  
I WANT to believe that all pathologists know exactly what they're
looking at all the time.  It's just not true, though.  My own
experience has validated his statement more than once.  The women on my
listserv who've had their own "HUH?" path-report-moments have also
seen the truth of it.   

MY EXPERIENCE:

BREAST TISSUE:
I sent my breast cancer slides to three different pathologists at
three different institutions in three different regions of the country.
 Though I no longer have the path reports themselves,  I remember how
puzzled I was that they seemed to have been based on three separate
sets of slides.  

The three agreed only in that there was invasive lobular on the
slides.  As to the other components, one said there was an area of DCIS
while the other two labeled this non-lobular part as two different
types of bc (It's been fourteen years and the reports drowned in the
flood following Hurricane Katrina, so I can't be more precise than
that.)

I know now that it's not as unusual as I thought it was at first.  Let
me point out that there's almost always uniform agreement when tissue
is benign.  That IS generally clear-cut.  

It's when the tissue is not or might not be benign that these
questions of "Well, what IS it?" arise, and the answers are not as
uniform as one would expect.  


MY EXPERIENCE
THYROID SLIDES

Six months ago, because there was a growing cyst on each lobe of my
thyroid, I went for a fine needle aspiration of one of the cysts.  

FIRST PATHOLOGIST: Possible neoplasm  (looks like it could be
cancerous)

ENDOCRINOLOGIST: Have it removed.
ME: Second path opinion, please.

SECOND PATHOLOGIST, same slides as the first one: Are you kidding? 
There's not even enough solid tissue on these slides to make an
assessment.  Get another biopsy.

ENDODOC: Get it removed.
ME: Another biopsy, please.

SECOND BIOPSY:  
FIRST PATHOLOGIST:  Benign.
SECOND PATHOLOGIST:  Benign.

I could have lost my thyroid altogether if I'd listened only to the
first pathologist.  

He called it as he saw it.  But so did the other guy.

Mind you, this is not a secret, Divinea.  It might not be widely
publicized, but pathologists are fully aware of these differences in
opinion.  

Pathologists at U.S. med schools and teaching hospitals are being
asked to work out clear-cut guidelines for their discipline, but it's a
work in progress.  It's not that easy to delineate exactly what an
invasive lobular cell looks like.  In GENERAL, yes.  But for a specific
cell?  Eep.  

It's not just in this country, either.  The call for better
regulations, clearer guidelines is happening in the UK, too.
  

    
I have to admit that I find it a bit confusing that you seem to be
maintaining that pathology is an inexact science, or "art", while you
also seem to be advocating thermography over mammograpy, while
thermography is, at least at this point, an unproven technology with no
established clinical standards. Can you clarify your reasoning?
  

    
#41 Pat Adams wrote,

          Perhaps this technology will be developed further:

         <http://gizmodo.com/5665071/what-is-this>


Y'know, you bring up a good point, Pat.  If computers could be brought
in to enhance mammograms as beautifully as this NASA-enhanced pic, AND
if they became part of the pathologist's arsenal, we'd see vast
improvements in diagnosis.

I don't know how feasible that is, but that NASA-enhanced image is
awfully impressive. If their enhancement technique involves picking up
what passes for heat in a mammogram, it might be the best of
thermography and mammography combined.  

Thanks for bringing that in, Pat.  

I won't hold my breath waiting for it to happen, but if it does, I'll
be very interested to see it in action. 
  

    
The tricky part of pathology of cancer is trying to predict when the
cells look enough like cancer cells that they're behaving like cancer
cells--ready to break out of their home tissue, invade the blood
stream, and set up metastases elsewhere.  If it looks like breast
tissue and it's someplace outside the breast, that's pretty clear.  And
healthy normal cells are pretty clear.  But just from looking at them
determining what is and what isn't cancerous can be very tough, even if
you have a few special stains available to look for extra things that
can't be seen in a regular H&E stained slide.

I'm not a pathologist but I've looked at enough tissue samples to know
that the kind of signals they're looking for can be pretty subtle. 
Their cytoplasm that does most of the tissue-specific work of the cell
shrinks, their nuclei get more irregular, and they start to look a
little more like a generic dividing machine than like a breast or a
thyroid cell.  They pile up irregularly instead of forming nice
structured ducts or glands or membranes.  Sometimes they outstrip their
blood supply and bits of them die and new irregular blood vessels
start to form.  By then it's obvious.  But the grey area between the
obviously cancerous and obviously benign is large and potentially
contentious, because cells don't come labelled 'cancer' or 'not
cancer'.  

I see a good deal of art within the science of pathology.

And thermography, if it can be standardized and consistently
effective, may be especially good for men who don't have breasts large
enough to squish in a mammography machine.  But as noted above, there
are a heck of a lot of fat guys of all ages out there who have breasts
of sufficiently generous size to fit the mammography machine.  I've yet
to see one actually join us in the mammogram waiting area, however.