Friday, December 4, 2020

SEMINAR TRANSCRIPT 1: IMAGE-GUIDED TRACKING PANCREATIC CANCER

INTRODUCTION

In patients with a family history of genetic cancers or who are otherwise at a high risk of pancreatic tumors, having the latest innovations and resources for identifying and tracking these tumors makes all the difference in every part of the treatment process.  Since we're trying to avoid radiation and biopsies at any time, we use ultrasound screening as the first line scan to image the pancreas. If there's anything suspicious we can employ the scanning feature that tracks the hardness of the cancer- where benign tumors are generally soft and cancers are generally rock hard. If the ultrasound elastic component demonstrates hard tissue and hence the likeliness of cancer that needs to be biopsied. In many countries, if the sonogram technology doesn't find that anything, then biopsies may be avoided. 


Click all slide thumbnails to enlarge 

Slide 1:  Image guidance tracking of cancer has been used internationally. When I first started in radiology, I went to finish my residency by going to Denmark to learn image guided biopsies under ultrasound, because they were not being done in the United States. And later, I went to Europe to learn blood flow imaging, which is turning out to be the most accurate way of determining cancer aggression.

Slide 2: The YELLOW EYE is JAUNDICE and that's often the first sign of cancer of the head of the pancreas because it blocks the green bile duct. Now you can see the rest of the pancreas is not connected to the bile duct. So cancer in these clinically silent areas often have no symptoms until it causes pain from wrapping around the blood vessels and nerves or has metastasized. 

Slide 3: In this simple sonogram, the head of the pancreas is labeled with two arrows. The body lies over the big blood vessel, the aorta which can be seen in seconds with high accuracy. Now the accuracy depends upon not only the experience of the person doing it, but also the equipment and the BODY HABITUS-  In other words, with very thin people, you get great images of the pancreas and in very heavy set people, we often have to resort to special imaging with ultrasound, but more commonly CT scans are considered the main way of imaging the pancreas in general practice.

Slide 4: As I mentioned, the vascular landmarks are key because the pancreas surrounds the great vessels shown in red and the stomach sits right above the neck of the pancreas. This is like a slice down the middle of the body. So it's a different orientation. You need 2 orientations in any imaging study to localize the cancer and triangulate the effects of the cancer on the adjacent organs.


Slide 5: Surgical landmarks show the liver on top and the arrows indicate the central  duct of the pancreas. So this is not the bile duct. This is the pancreatic duct, which is different. And in this case with a simple ultrasound over the abdomen is two millimeters thick. It is as thin as a dime.  Note that the teardrop vena cava, which is the huge vein. Again, the vessels are key because tumors that invade tend to block the great vessels 

Slide 6:  The French perfected the pancreatic treatment using chemotherapies. By using chemotherapy, they were able to shrink the generally large tumor, by the time it was diagnosed to something that was operable. The bottom of figure one on the left shows it's resectable. If it is sparing the aorta (a great blood vessel) and the far right shows that anything forming or invading the great vessels significantly is considered nonresectable. Fortunately advanced therapies can shrink it--  so a resectable tumor can be extracted from a non resectable mass using radiation chemotherapy or other cancer treatment technologies.

RESECTIBLE means that it is operable. That is, if it's hitting the next two, but partially invading and not completely invading the aorta or the vena cava or into the major structures in the middle of the abdomen that the pancreas surrounds, you can cut it out with a scalpel.  And to make it resectable or operable,  we use treatments such as chemotherapy or radiation or now immunotherapies to shrink it so it becomes operable and cut it out and hopefully curative with an operation. 


Slide 7: In 2011, the cancer commission based treatment on the size of the tumor and it, the second edition at the bottom, they talked about future biologic markers and other factors. This way, we were able to use genomic testing and blood vessel imaging.

Slide 8: Staging in 2019 uses other cancer markers and a more personalized approach based on the patient rather than on a formula or a paradigm, dictated by the medical profession that  strategizes a standard treatment approach. This now includes gene testing and advanced vessel imaging technologies which measure and quantify how many tumor vessels are invading the area or how many cancer vessels are supplying the cancer and making it grow. 

Slide 9: Nodal Staging- in the case of jaundice, the head of the pancreas cancer shows up as yellow eyes because it is obviously blocking things. However, often the first sign of a cancer in the body, neck or tail of the pancreas shows up as a lump in the neck, a mass under the arm, or a painful irregular mass in the groin. These are lymph nodes. Lymph nodes can be staged to according to the classic criteria.

Slide 10: Once you find that a mass contains lymph nodes, we have to see if it's an abnormal lymph node, and then what part of the lymph node is abnormal.  Is it inflammatory? - Or is there a fatty replacement?  Are there two lymph nodes stuck together? So the ultrasound is the simplest way to study the lymph nodes because the patient often will take the probe in his or her hand and put it on the area that’s hurting or growing fastest.

Slide 11: Because the sonogram can target the biopsy, we can check which part of the mass, be it in the arm, groin, neck or any other place in the body where lymph nodes tend to occur and are accessible by the surface. So this excludes lymph nodes deep in the pelvis(?) or around the great blood vessels that have to be imaged by CT or MRI.

We target the lymph node by doing guidance to advance the needle into the  most suspicious part of the biopsy site.  Guided biopsy under ultrasound is the best way to extract the cells and get a diagnosis. This means that you do not have to cut out the whole lymph node  and send it to a pathologist. We put a tiny needle in under sonogram guidance (or  CT or MRI), extract a core of cells and give it to the cytopathologist who's sitting in the same room for immediate pathologic confirmation. 

Slide 12: Looking ahead, the cancer organizations are now focusing on tumor biology and cancer markers. There's something called radiomics, which is using radiology and the appearance of the image to decide how aggressive the tumor is.  , Radiomics means the size, the shape, the vessel density, or tumor blood flow—that’s blood flow of cancers flowing into the tumor which can be measured either by the Doppler ultrasound, by contrast CT, or CT with dye to show the blood vessels going in, or contrast MRI- which again is another way to look at the tumor vascular flow, which is the best marker of  cancer aggression. This is so important that when we treat cancers, we use the blood flow to see if whatever treatment you're using has killed them off- such as in freezing or radiation or with the new laser treatments. 

The other part of radiomics is the hardness of a tumor.  Cancers are usually hard, and this is called the elastic properties. So radiomics and cancers encompasses many parts to the imaging features. 

Slide 13: Cancer often goes to bone and frequently to the spine. The ribcage being a very common area. This metastatic focus to the eighth rib is clearly seen with the red arrow pointing to it. The image to the left of that shows tumor blood vessels and then in the bottom, right, is something that is called a histogram indicating a Vascular Index, 47%. This is a measure of how many cancer vessels are in this particular area, which is again, a measure of aggression, a quantitative indicator of how aggressive the tumor involvement in this volume is. And once you have a quantitative measure is, could be used as a guide to treatment follow-up. 

Slide 14: The Vessel histogram technology is the use of 4D imaging. This means we look at the tumor in real time. 3D imaging shows the entire tumor and the 4D aspect means we search around to the most aggressive area as seen in the left side of the picture. 2D Doppler simply shows blood vessels and the right 4D image gives you an indication of the tumor biology in the moment-the  red part is vascular and dark part is cystic or avascular. And more importantly, if something is avascular or cystic, there are no tumor vessels in it because the tumor in that area is dead.

Slide 15: This is an example of the use of vessel density. In this case, there is a patient with a previous cancer. There's a large mass under the arm.  On the top right, if you put a needle into the vessel density 1%, you're going to get useless, bloody fluid. If you put it into the area, that's 27% vessel density, you're going to get usable pathologic material instead of an inconclusive biopsy.  You're going to get cellular material for tumor markers and genetic analysis. Histogram vessel imaging takes only minutes to perform on a computer workstation and is a process that’s widely used worldwide

Slide 16: An example of cancer treatment being adjusted or followed or analyzed by tumor vessel imaging is Adenocarcinoma, which is the usual cancer in the pancreas. The top image shows  this non-treated specimen. The graph shows the vessel density at 32.9%.  This patient opted to be treated with complementary methods. A lot of people come to me because they refuse surgery and want to try natural or minimally aggressive alternative or even experimental  treatments. We can see that six weeks later, the alternative treatment worked because the vessel density went down from about 33% to 5%. As a followup, two months later, the patient stopped the treatment and the vessel density went back up to 23%. Again, following treatment, some months later, the tumor vascular index or vessel density went down to 8.1%. So what the quantitative means of noninvasively telling if a cancer therapy is working or not is a realtime validation of success because you've got the tumor and the treatment effect in front of your eye, and as long as the picture is accessible by imaging technologies as most of them are, this is a useful way to tell the patient that the treatment is working or not working--  so you can change treatment in a timely matter.

Slide 17: Now as far as imaging, we have established procedures, diagnostics such as biopsies and needle aspiration and angiography using the blood vessels to show where the tumor is by x-ray. And in the future, we'll be using more molecular imaging technologies where you can image tumor marker cells without using standard X-rays.  On the therapeutic advamces, we are now using ablative or killing technologies such as thermal technologies, that is, heating a cancer with radio frequency or microwave or lasers to kill it.  There is chemoembolization of cancer where you block the blood supply to a cancer, which makes the cancer die.  There’s also radiation therapy, external and now internal or intra-operative radiation where the radiation seeds are stuck inside the tumor and xrays are not delivered outside of the body. These are being done now. 

 I won't get into palliative options, but there are many ways to deal with complications. And also in the future with therapy, we're using hybrid technologies that is using MRI  fusion with ultrasound, using CT with genetic tracers, and intra-operative injection of tumor killing drugs that is directly into the body of the tumor rather than induced intravenously.

Slide 18: Also great advances are being made in immuno-oncology. We evaluate the patient personally, explaining the pros and cons and use different criteria for identifying the anti-tumor immunity and the technique of delivering the treatment. Once again, everything depends upon the imaging to see where the tumor is and making sure that the tumor is responding succesfullly. The side effects of some immuno-oncologic treatments are fairly severe, so if a treatment is not working effectively quickly, we can switch to another treatment application. 

Slide 19: Genetic testing overall has 60% accuracy. For example, the study from Memorial Sloan Kettering showed in melanoma diagnosis, there was 55 to 63% accurate in a year long study.  Gene tests in the pancreas have a similar accuracy to the clinical testing. Your risk is increased if there is a BRCA gene positivity in the family or there's other genetic and family disorders such as the Lynch syndrome and  PUETZ-JEGHERS syndrome, which caused a high incidence of GUT related tumors or GI related cancers such as colon cancer and small bowel cancer.  


Now if somebody has a history of Lynch syndrome or PUETZ-JEGHERS or other significant genetic markers, then we follow the patients. Remember,  pancreatic cancer (unless you have Jaundice) is commonly invisible until it causes systems like paralysis, vertebral collapse because the bone is invaded or your legs swell because the big blood vessels are blocked or thrombosed by the tumor. So the idea for screening is to find it early with minimal harm and minimal radiation. So now MRI and endoscopic ultrasound screening are recommended for these in the United States.

Slide 20: Now in the rest of the world, other technologies are used, for example, in 1974, when I trained in Denmark, the surgeons there were doing imaging.  They were actually putting needles into a pancreatic mass through skin within the local anesthesia to get the sample of the tumor. This was forbidden in the United States until 1999, and now  used sparingly. American guidelines do not do not like image guided biopsies for some reason, but the rest of the world does it. The same thing with Elastography. This is not being used in many other areas. This slide shows that the pancreatic tumor can be seen with multiple technologies. The bottom image on the left (A), the green area shows that the tumor is benign or is a fatty tissue.  To the right of that is a small dark area on the sonogram. And interestingly, the last image (D) is done with a hand held portable ultrasound unit that shows a 1 centimeter mass in the body of the pancreas.

Slide 21: Contrast the sound is again, being used all over the world and it shows the cancer vessels where the tumor vessels feeding a cancer- in this case, a pancreatic tumor, and the blood flow shows up in seconds- following intravenous contrast, which is safe. 

So unlike the CT or the MRI contrast, there are no side effects from contrast ultrasound. 

Slide 22: The contrast MRI shows the white arrow pointing to a huge pancreatic mass. And this is the common way that pancreatic tumors are assessed using MRI and contrast to show the location and pre-surgical planning of pancreatic cancer procedures.

Slide 23: CT staging with molecular biology or radioisotopes is used to find the tumor and to stage it. In other words, the pet CT is a radioactive tracer study to show where the tumor is- and if it's getting better. An example (A) on the left, you see the tumor under the arm and a follow-up study some months later shows that the tumor has spread. This is an indication that when you look from one black tumor dot to three larger tumor dots in the same order that treatment should be readjusted.

Slide 24: With Elasto-Endo ultrasound, benign tissue is green. The liver tissue is blue. This is a technology that's been used for 30 years. And in cancer screening worldwide, it's been used to avoid biopsies and the breast by road, skin, prostate, pancreas, and liver, or to biopsy simply based on the color of the elastography image. It's highly accurate. And it's used as a primary screening tool more and more. So elasto-endo ultrasound means that you're putting a tube like an upper GI series or an endoscopy, where they put the tube into the duodenum and use the probe to image the affected area of the pancreas. While this is an invasive procedure, it avoids biopsies sometimes.

CONCLUSION: Teamwork helps to get the job done even if all the participants involved aren't necessarily individually and separately, compatible- but as a team, it's way to go. It works very well. Thank you.



ROBERT L. BARD, MD, PC, DABR, FASLMS
Advanced Imaging & Diagnostic Specialist
Dr. Bard received the 2020 nationally acclaimed Ellis Island Award for his lifetime achievement in advanced cancer diagnostic imaging. He co-founded the 9/11 CancerScan program to bring additional diagnostic support to all first responders from Ground Zero. His main practice in midtown, NYC (Bard Diagnostic Imaging- www.CancerScan.com) uses the latest in digital imaging technology and has been also used to help guide biopsies and in many cases, even replicate much of the same reports of a clinical invasive biopsy. Imaging solutions such as high-powered sonograms, Power Doppler Histogram, sonofluoroscopy, 3D/4D image reconstruction and the Power Doppler Histogram  are safe, noninvasive, and do not use ionizing radiation. 


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