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Archive for the ‘Brain Tumors’ Category

Sunday, December 8th 2013

Awake Brain Surgery

Sometimes as a matter of a tumor’s (or other lesion’s) location within the brain it is helpful to have a patient awake for part (or all) of the actual removal of such. It aids staying away from important normal parts of the brain.

Similarly, I’ve been doing/seeing a lot of deep brain stimulator surgery lately and having the patient’s awake can aid in making sure the lead is in the right spot, or at least not in the wrong spot.

It is pretty incredible to see.

Saturday, December 7th 2013

Novel Treatments

The history and evolution of novel clinical research is interesting. The old ideal, “Don’t think; try is, perhaps rightly tempered by the new ideal of not just the informed and consented patient but protected patient. Such is interesting considering our move, otherwise, away from paternalism.

The development of the smallpox vaccine or the first artificial heart would have never happened today as is. Of course, neither would these horrific syphillis experiments hopefully.

Not to argue that IRBs and government agencies have made clinical research too burdensome and are hampering progress.

It’s just that a focus and regulations beyond guaranteeing informed consent seems counter to the way the rest of medicine is moving.

I’m not sure many are arguing three glioblastoma multiforme patients of Drs. Muizelaar and Schrot were at UC-Davis were ill informed. But the treatments they undertook for those patients, without approval, have cost both men their jobs. Dr. Muizelaar was in fact chairman of Neurosurgery at UC Davis prior to this scandal bringing him down.

I’ve covered this previously. But with both men resigning earlier this year its worth bringing up again now that we have some resolution.

Two UC Davis neurosurgeons who intentionally infected three brain-cancer patients with bowel bacteria have resigned their posts after the university found they had “deliberately circumvented” internal policies, “defied directives” from top leaders and sidestepped federal regulations, according to newly released university documents.


The most contentious issue between the doctors and the university – and even within the university – was this: Were the surgeons performing research? Or were they providing “innovative care?”

Research on humans is tightly controlled in the United States and, according to federal regulations and university policy, must undergo a rigorous approval process to ensure that participants are protected from harm. Innovative treatment, more commonly known as compassionate care, gives a doctor more latitude in offering nonstandard care to a single patient where evidence of safety or success is limited.


Muizelaar and Schrot called their novel approach “probiotic intracranial therapy,” or the introduction of live bowel bacteria, Enterobacter aerogenes, directly into their patients’ brains or bone flaps. The doctors theorized that an infection might stimulate the patients’ immune systems and prolong their lives.

The first patient lived about 5 1/2 weeks. The second survived another year, an outcome that buoyed the doctors and seemed to bolster their theory, they said.

The institutional trouble began in March 2011, when a newly diagnosed third patient developed sepsis, became unresponsive and died two weeks after being deliberately infected. The university’s first internal investigation soon followed.

What they did was highly unethical and dangerous.

But I have trouble with this paternalism later in the article,

“I think sometimes surgeons and doctors can get caught up in the enthusiasm for what they really believe is going to work,” said Caplan, head of medical ethics at New York University’s Langone Medical Center. “That is exactly why we have FDA oversight and approval and the research ethics requirement we do.

“Every time somebody dies or is injured or we have to recall a product, what we find ourselves saying is, there is no short-cut to innovation,” he said. “Finding the truth is a long, slow, arduous process.”

Informed consent for novel treatments can be difficult. “Informed” consent for proven standard of care is difficult. But maybe the focus should be on that and not necessarily on impeding access to even highly dangerous and unproven treatments.

Tuesday, June 4th 2013

Some Disappointment For Avastin

Bevacizumab is an anti-VEGF antibody used as a chemotheraputic agent. VEGF is a growth factor in the body that promotes the growth of new blood vessels. The antibody is marketed as Avastin and has on-label approval in a number of cancers. Initially approved for colon cancer it is now used in lung and renal and, for our purposes in this post, glioblastoma multiforme. GBM is an aggressive primary brain tumor. It is what Ted Kennedy passed from.

Avastin got quick approval for GBM from the FDA based on limited studies and results that showed it delayed progression once patients had progressed on traditional chemotherapy.

Well now at the American Society for Clinical Oncology meeting two phase III randomized studies have shown somewhat disappointing results for Avastin in terms of prolonging overall survival in patients with GBM. Both the Radiation Therapy Oncology Group protocol and the AV Aglio trial put Avastin with Temodar and radiation therapy at diagnosis to see if such improved survival versus simply temodar and radiation, a more traditional therapy. Perhaps no surprise as phase II trials had shown similiar prior to these two large trials but there was no improvement in overall survival.

Avastin didn’t prolong life when used as a first treatment for people with brain tumors like the one U.S. Sen. Edward Kennedy died of several years ago, two studies found. In one, patients who were expected to benefit the most from Avastin based on genetic testing had the worst survival rates. Side effects also were more common with Avastin.

That might not be so horrible, since Avastin’s current approval is essentially as salvage, but the side effects were much more significant when Avastin was added to Temodar as a first line agent.

Avastin used to have approval for use in breast cancer but something very simliar had to the data with Avastin in breast cancer that prompted the FDA to pull approval.

Avastin received Food and Drug Administration approval after studies suggested it delayed disease progression. But when later research showed it didn’t prolong life and brought more side effects, its approval for breast cancer was revoked.

I would argue, and clinicians more in the know than myself however are already as well, that progression free survival in brain tumors is something different than progression free survival in breast cancer patients.

[B]ecause of the cramped quarters of the brain, progressive disease almost always has immediate effects on cognitive and motor functions. Other studies have shown that patients receiving Avastin are more likely to be able to live independently, and have less need for corticosteroid drugs.

If Avastin does indeed produce very quantifiable quality of life benefits, potentially mostly in terms of preserved cognition and functional ability, then it would obviously be a potentially well worth therapy, at least as continued second line therapy, even with its known potential side effects.

Monday, May 27th 2013

Playing A Guitar During Brain Surgery

It is common practice in some techniques for putting in deep brain stimulator electrodes to keep patient’s awake to make sure the electrode is in the right place and giving good symptom relief. Likewise for parts of some surgeries for brain tumors you might have a patient awake to “map” their brain surrounding the tumor so as to not damage important parts that control things like movements or speech. You may ask patients to do certain tasks while they’re awake so that you can see if the stimulation is working or see if an area of the brain is involved in such a task. I don’t think I’ve ever heard of anyone playing the guitar during a surgery however.

Sunday, May 5th 2013

Facing The Truth On Cancer

You need to read this piece in Salon by Mary Elizabeth Williams who is living with widely metastatic melanoma.

[T]he fate of people with metastatic cancer is the same as everybody else’s – to go on living until life ends

It raises important issues, and links to posts from others on the same subject, about how the end of life with cancer makes even cancer patients and cancer support groups and cancer researchers uncomfortable.

Monday, July 23rd 2012

Research At Your Peril

A physician can’t employ novel, potentially dangerous, treatments on you, even with your permission, without crossing off Institutional Review Board approval. The IRB critique process is designed to weight the risk/benefit of the proposed study and assure appropriate informed consent of the subjects. And in the case of new drugs or devices, the physician can’t do it without running through the Food & Drug Administration.

And so the confusion out at UC-Davis right now, involving the chair of neurosurgery, is likely to grab some attention.

In 2008, [UC-Davis neurosurgery chair Dr. J. Paul Muizelaar and his colleague Dr. Rudolph J. Schrot] proposed treating a glioblastoma patient with bacteria applied to an open wound to “attack the tumor,” then later withholding antibiotics and letting the bacteria do its work.

Schrot contacted the FDA but ultimately was cautioned that animal studies were needed first.

Back at UC Davis, IRB chairman [Dr. John] Anderson…was also skeptical. Anderson told Schrot in an email that denying this patient the treatment would be “likely devastating to this family,” but that he believed the FDA and UC Davis “won’t allow this product to be used in humans without further testing,” internal documents reveal.

Despite the initial roadblock, Muizelaar and Schrot “strongly believed that the intervention with intentional wound infection was promising for patients who otherwise faced certain death,” according to [a letter from Harris A. Lewin UC-Davis' vice chancellor of research]


Between October 2010 and March 2011, the physicians went forward with three procedures on humans with malignant brain tumors, surgically introducing probiotics into their open head wounds.


Schrot got IRB permission to move forward on Patient No. 1 with a “one-time procedure” that was “not associated with any research aim,” the letter states.

University documents show that the physicians believed they had been given the go-ahead for all three surgeries, but officials later determined that they had been misinformed or were misunderstood by the doctors.

Muizelaar and Schrot stressed to The Bee that all three patients, in consultation with their families, gave their consent.


In the case of Patient No. 1, the investigation found, Schrot had made an “incorrect statement” about restrictions on the bacteria’s use, leading IRB staff to incorrectly conclude that such review was not necessary, Lewin told the FDA.

As for Patients 2 and 3, the university found that treating them with an “unapproved biologic” amounted to human-subjects research – and thus required prior review and approval.

The idea of infections stemming cancer progression is hardly unprecedented and is reported in the literature for everything from lung cancer to bone cancers. Indeed, even intentional infections in cancer patients have a history. And, although two recent relatively large retrospective studies from 2009 and 2011 failed to show post operative infections improved survival in GBM, the issue remains equivocal with more anecdotal reports supporting the idea that infections may promote an immunologic response against the tumor itself.

Much of the issue seems to center on the idea of these bacteria as a ‘biologic’. If what Drs. Muizelaar and Schort did constituted ‘research’ of a biologic then there is likely real trouble ahead and much, if not all, of UC-Davis’ federal research funds, from all sources, could be at risk. It probably bodes well that if the University thought there was something wrong going on here that they self reported it and potentially did so in a relatively timely fashion.

I’m not going to jump to conclusions here. Although two patients seems to have had poor outcomes, potentially related to the treatment, it seems very plausible that this is a matter of bureaucratic misunderstanding. I understand the idea behind IRBs and the reasoning of a level of paternalism that most bioethicists feel patients need,

Arthur Caplan, director of medical ethics at New York University’s Langone Medical Center, said that desperate people are especially vulnerable and need added protections.

“If you’re dying, you’re kind of like reaching out to anything that anybody throws in front of you,” said Caplan, who recently left the University of Pennsylvania’s Center for Bioethics to assume the New York post.

“That’s why so many people over the years are pursuing quack cures in Mexico and all kinds of questionable treatments,” he said, speaking in general terms. “They’re not able to think straight because they’re at death’s door.”

Caplan said that institutional review boards are often misunderstood, with many people believing that such strenuous oversight is “a lot of bureaucracy to get in the way of trying something to save lives.”

In reality, he said, the committees are an essential safeguard for research subjects, who may not get an unbiased view on a researcher’s consent form of the study’s risks vs. benefits.

Maybe the informed consent portion should be the sole purview of the IRB. It is true that the ‘informed’ in informed consent can be a matter of contention, there is very often a wide discrepancy in information between a provider and patient. However, if Drs. Murzelaar and Schort, provided a reasonable view of the risks versus very potential benefits to these patients, even if the use of the bacteria actually under law fell to the FDA for permission, I would be inclined to step back, take a very libertarian view and think much unnecessarily is being made of the situation.

I’m sure fuller details are to follow. It is unfortunate that this is playing out so publicly at present.

Monday, July 2nd 2012

International Care From Socialized Medicine

An interesting piece on ‘rationing care’ in single payer systems. The piece in The Guardian focuses on British patients who are sent overseas for specialized therapies not available in the United Kingdom, with the trips funded by the NHS. And how that compares to the current U.S. system.

Ethan [who has an ependymoma] is in the US because the NHS as yet does not have proton therapy machines, although the UK government has just agreed to fund two of them, in London and Manchester.

Pay for service models will obviously be inefficient and provide a plethora of potentially unnecessary care. There are probably strategies to mitigate the inefficiency of over use in a fee for service system, but they will never be as effective as the central control afforded in a single payer system.

The scary thing about such overt rationing, as in the NHS, is it removes some control from the patient and their personal physician and puts the control in the hands of committees of amorphous physician ‘experts’ and bureaucrats who deem what is appropriate and available care and what is not. The great fear is that such a system will deny effective or questionably effective care as a matter of cost.

The reality is that the U.S. system already does this. Private insurers already deny payment for treatments as being unproven. Centralizing this rationing and making it more transparent and overt may be an answer. Certainly it seems the case with the NHS and proton therapy.

Wednesday, May 9th 2012

Livetweeting Surgery

One of the big things the use of social media in medicine is supposed to do is help diminish the information disparity between providers and patients. Although knowledge asymmetry is present in many fields perhaps nowhere is it as large as in medicine. If you’ve never been in a surgery I can do all I can to explain it in an informed consent process but perhaps hearing about it, seeing it in real time.

That said I though the novelty of using social media during surgery would’ve died down by now. As well as its use. Its not like the social media observer experience has been widely adopted by patients. I’ve never run across a patient in practice whose referenced having used social media to experience surgery as part of their information gathering process. Not that I think the effort is fruitless but the whole ‘live’ experience is overstated. In effect these livetweets of surgery are a publicity stunt.

And yet, here we are in Houston with a proposed first use of Youtube and Pintrest in a livetweeting of a brain surgery.

“What will come out of this is a detailed, real-time sequence of what happens in a brain surgery through all the stages from preparation, to shaving the hair, to making the incision, to draping,” Dr. Kim says. “People are very anxious and want to know what goes on in a brain surgery like this.”

While Dr. Kim (left) works in the operating room, a team outside the room will work the social platforms. A brain tumor specialist will be present to help answer questions from the digital audience via Twitter. But the operation will expand to other social networks too.

Video clips from inside the operating room will be posted to YouTube, and photos shared on Pinterest. Storify compilations will recap each hour of the broadcast.

A big enough story to prompt Mashable’s attention and CNN and Medgadet.

The web and social media are a great source of information for patients and families of all types, including those facing surgery. I applaud providers and hospitals and others for putting such information out there and using social media. The live presentation of that information though and, especially, the hype surrounding such seems overdone. Five years from now we will neither be giving fanfare to livetweets of surgery nor will be doing it on a regular basis. In some respects it seems a waste of resources in using social media and the internet to distribute information.

If you want to tune in though the livetweet begins today at 9am central time and can be found @houstonhospital.

Monday, December 22nd 2008

A Mature Tumor

While I was away on the interview trail a very interesting story hit the media wires. In Colorado a pediatric neurosurgeon went in to sample/remove a tumor from a young child’s brain. What he found was that the tumor contained fully formed anatomical parts. Included was a fully formed foot.

“It looked like the breech delivery of a baby, coming out of the brain,” Grabb said. “To find a perfectly formed structure (like this) is extremely unique, unusual, borderline unheard of.”


Sam’s parents, Tiffnie and Manuel Esquibel, said their son is at home now but faces monthly blood tests to check for signs of cancer or regrowth, along with physical therapy to improve the use of his neck. But they say he has mostly recovered from the Oct. 3 surgery.

“You’d never know if he didn’t have a scar there,” Tiffnie Esquibel said.

The question is how did this happen.

The Foot In Surgery

Teratomas are a type of germ cell tumor which can occur in the brain. They develop from embryological cell lines and often develop characteristic mature tissue including skin, hair, teeth. Cases have certainly been reported of even more complex structures appearing in teratomas, including eyes. Approximately one hundred cases of a situation called fetus in fetu have been reported. In such cases a born child ends up having parts of his assumed twin growing somewhere inside of him. Fetus in fetu often have even more complex structures, including what often appear as fully formed limbs and organ systems. As in this case.

I’m not sure if a case of fetus in fetu has ever been reported inside the cranium. Still, teratomas often occur there and in some people’s opinion fetus in fetu should be considered a highly rare form of teratoma. In anycase, this is an incredibly rare and interesting discovery. My thoughts are with the family but if the AP report is to be believed the kid is doing well.