boas

Immunotherapy can help the immune system attack cancer cells, but it often works poorly for liver metastases, where immune responses are naturally suppressed. This study proposes a new way to deliver immune-stimulating drugs directly into liver tumors via the tumor’s blood supply, using drug carriers that slowly release the drug into the tumor over time (immunoembolization). We developed and tested several different drug carriers, including microspheres and emulsions, and showed that the immunotherapy drug is released into the tumor over days to weeks, resulting in liver tumor shrinkage in pigs. Extended-release immunoembolization has the potential to maximize immune activation in liver metastases (in situ vaccination) while reducing autoimmune side effects.

The latest publication from my lab is a new intratumoral immunotherapy delivery platform, which achieves 6 days of intratumoral drug release, from a single injection. Tumors can be “painted” with drug using a needle, and the drug stays exactly where it’s injected, maximizing immune activation in the tumor, while reducing systemic toxicity.

The immune system is like a computer, which uses chemical signals, instead of electrical signals. When the immune system sees a potential threat, it needs to integrate information from multiple sources, to decide how to respond. Making the correct decision is important for fighting infections, killing cancer cells, and avoiding autoimmune diseases.

To manipulate a computer circuit, you need to deliver time-dependent electrical signals to a specific location in the circuit. To guide the immune system into attacking cancer cells, my lab has been developing new technologies for timed local delivery of chemical signals. Spatial control is achieved by image guided delivery into tumor versus lymph node. Temporal control is achieved by programmable multi-drug release kinetics from the drug delivery implant. Different drugs can then be delivered into specific locations at specific times, to convince the immune system to attack cancer antigens.

Instead of major surgery, tumors can be treated by blocking off the artery supplying the tumor, thus starving the tumor of nutrients and oxygen. This is a common treatment for liver tumors, and this paper now shows that the same thing can be done for pancreatic tumors.

OpenSCAD file for the barbed catheter:

https://static-content.springer.com/esm/art%3A10.1038%2Fs415...

When the immune system encounters a new antigen, it needs to make a decision about whether to attack, or to ignore. Making the correct decision is important for fighting infections, killing cancer cells, and avoiding autoimmune diseases. The decision is made using time-dependent chemical signals and computations that occur at different places (tumor, lymph node, blood).

So if we think of the immune system as a computer that uses chemical signals, rather than electrical signals, how do we communicate with the immune system, to help it make the right decisions? My lab has designed a catheter that allows us to deliver time-dependent chemical signals into tumors and lymph nodes. The catheter contains a 3D printed retention mechanism to prevent migration, and it is implanted using image-guided, minimally invasive techniques. Different drugs can then be delivered into specific locations at specific times, using programmable pumps, to convince the immune system to attack cancer antigens.

That's the system we had in the 1970s (government owned the patent to government-funded research). And what happened is that the government didn't know what to do with the patents, and the inventors, who were best positioned to commercialize their invention, could not justify spending time and money to commercialize something that they didn't own. So the Bayh Dole act of 1980 allowed universities to commercialize their federally funded inventions. The result was an explosion of startups, especially in the biotech industry.

Example: John Adler received some government funding to develop Cyberknife (image-guided radiation therapy). But he couldn't get follow up funding to commercialize this revolutionary new technology. So he took out a second mortgage on his house to commercialize the invention. And now image-guided radiation therapy is a standard treatment for many types of cancer. There's no way he would have taken out that large personal loan, if he didn't own the intellectual property.

There's a large gap between a patent, and a commercially viable product. And if you showed the patent to "experts" in the field, they would likely tell you that it's worthless. Great ideas are only obvious in retrospect. The inventor has the vision, motivation, and knowledge to make their invention a reality, but they can't quit their job and get external funding, if they can't own their invention.

> Life would be simpler if only these hospitals could set aside their arrogance and just go with the recommended workflow!

This would be like asking programmers to standardize on the recommended programming language.

we would love to just use the recommended workflow, if it worked for our hospital. There are differences in the patients, doctors, local regulations, existing systems, etc between hospitals.

Patients: Top cancer hospital does a lot of clinical trials, so some of the forms require you to fill out clinical trial information for every patient. In a maternity ward, it would not be appropriate to ask about clinical trials for every patient.

Doctors: Hospitals are staffed differently. If the hospital has residents, some of the work can be delegated to residents. If not, someone else has to do it. The workflow needs to account for who is actually available to do the work.

Local regulations: Medicine is highly regulated, and each state and hospital has its own rules.

Existing systems: Hospital computer systems have been around for decades, and usually it's not possible to migrate everything to a new system, so the new system needs to integrate with the old systems that couldn't be upgraded.

In a hospital or healthcare system, all of the doctors can generally see all of the imaging, labs, and notes for all patients. The problem with "curbside consults" -- where another doctor provides an immediate opinion without seeing the patient -- is that 1. The other doctor often doesn't get the full picture without doing a full evaluation. 2. Increased malpractice risk 3. It's not billable.

I'm a doctor, and in my own experience, my first impression from just seeing the images and talking to the other doctor is sometimes completely different from my final opinion after reviewing the chart and seeing the patient.

Wait times are also a problem, because hospitals and clinics like to operate at close to 100% capacity. There are huge fixed costs in a hospital, and hospital profit margins are often <5%, so that's why they have to operate near capacity.

Interventional radiologist here. The short answer is "no." I personally perform more than 100 different types of procedures, but there are lots of variations of each procedure, and different techniques for performing the same procedure. (And you need to know what to do when something unexpected happens in the middle of a procedure)

There are thousands of CPT codes, and even more procedures, since one CPT code could describe multiple different procedures, and some procedures involve combining multiple CPT codes. There is no formal approval process for new surgical procedures, and there is no comprehensive list. New procedures are invented all the time.

Your best bet is to pick a specific area, then find a surgeon to shadow. A lot of details of surgical techniques are not written down anywhere, and you learn by working with other surgeons. There are a few books that go through the basic procedural details. For example, Zollinger's "Atlas of surgical operations" is a good reference for abdominal surgery, and Kandarpa's "Handbook of interventional radiologic procedures" is a good reference for interventional radiology procedures. "Biodesign" by Zenios is a good introduction to inventing new medical devices.

Another thing to keep in mind is that “one” procedure often involves multiple CPT codes. Sometimes the CPT codes change during the procedure, based on what the surgeon finds. The hospital should be able to give you an estimate of the cost. Ask your surgeon to help if you are having problems getting information.

Yes, we induce pancreatic cancer in pigs, and then we try to treat the cancer.

One important question is why so many new cancer treatments are successful in mice and rats, but then fail in human trials. You could point to genetic differences between mice and humans, but I think another important factor is simply the size difference. Just like a scale model of an airplane won't fly the same way, there are also scaling laws in animals. Large animals have a lower metabolic rate (per kg), require lower drug dosing (mg/kg), have more defense mechanisms against cancer, and have differences in blood flow and many other variables. We suspect that cancer treatments that work in pigs will be more likely to also work in humans.

We've tried the organoid approach, but ultimately, you need an animal model to properly model blood flow, immune response, etc. So we developed a pig model of pancreatic cancer: https://journals.plos.org/plosone/article?id=10.1371/journal...

My lab uses an engineering approach to develop new minimally invasive cancer therapies, and some of the new therapies are already being translated into early phase human trials: http://www.edboas.com/lab/

We're hiring biomedical engineers, so please contact me if you're interested.

If the fluoro (X-ray) machine fails during a procedure, you can either bring in a portable C-arm, or move the patient (mid-procedure) to a different procedure room with working equipment.

If the power goes out and the backup generator fails during a procedure, people take out their cell phones and use the flashlight. If the patient is intubated, you can manually ventilate the patient.

If the equipment you need for an emergency procedure is not working, there is often an older, lower tech method to do the same procedure, or at least stabilize the patient.

If the electronic medical record system goes down, you can use pen and paper. Those records are then scanned in or entered into the EMR when it's back up.

Unexpected things happen a lot in medicine, so it's good to always have contingency plans.

Source: I'm an interventional radiologist.

p value by Fisher's exact test is 0.007. It's a significant difference.

> Vista[0] (the VA's EMR) is pretty scary. I wouldn't wish it on anyone.

why do you say that? From a doctor's perspective, Vista is one of the more user friendly EMRs.

Here's a normal brain MRI, compared to photographed slices of a brain:

https://www.claripacs.com/a.php?a=vw (Click and drag to scroll. "Share > Download" to download the full DICOM data)

This site has thousands of anonymized MRI and CT images of normal and abnormal scans, with clinical history in many cases. For example, here are annotated scans of normal anatomy:

https://www.claripacs.com/folder/Anatomy&view_type=-1

One challenge with writing web DICOM viewers is the lack of full 16 bit image support in browsers. This requires writing custom code to properly handle window / level on 16-bit medical images.

Disclosure: I'm a co-founder of Claripacs.

Thanks! I'll look into this. I also use g++ on Linux, so a cross-platform solution would be nice.

A lot of the radiology software that I write involves iterating over a 3D grid. The auto-parallelizer lets you easily process each 2D slice on a different processor core. My laptop has 2 cores x 2 hyperthreads per core = 4 virtual cores, so 4x speedup.

I wish that on AWS, you could create EBS volumes larger than 1 TB. I know you can set up RAID to get > 1 TB, but it'd be nice if Amazon handled this automatically.

We developed an easy way to email and collaboratively view CT or MRI studies. http://www.claripacs.com.

The US post office is amazing. They can deliver a letter cross country, door-to-door, for 46 cents! In my experience, USPS and Gmail's spam filter lose important mail at similar rates, < 1%. This is based on how frequently my credit card bills are lost.

Do you sign business associate agreements with your colo facility, ISP, and landlord? They also are physically capable of accessing your data, even though they are legally or contractually forbidden from doing so.

According to Amazon, their employees are not allowed to access to your data, so you don't need to sign a business associate agreement with them to be HIPAA compliant. I imagine this is similar to how sending patient information through the post office is not considered a disclosure to the post office.