Diagnosing Pancreatic Cancer using a PET Scan

Image Above: Figure A: an anterior view PET scan of torso.  Figure
B: transversal view PET scan of torso.  Figure C: pancreas with the
head of the pancreas almost absorbing all of the tracer.  Figure D:
whole pancreas up taking tracer.  Figure E: Tracer is excreted into
other organs, which cause them to appear on the PET scan (1).  

As of now detection of pancreatic cancer remains as a very difficult task. Pancreatic cancer is often not diagnosed until stage III or IV and the cancer has often already metastasized.  On top of this, most cases of diagnosing pancreatic cancer involve very invasive methods. However, a scan known as positron emission tomography (PET) is a great method for imagery of the body due to its non-invasive nature and can be specified for tissue metabolism (using the tracers) rather than on tissue mass or x- ray absorption. Thus, an increase in glucose metabolism, a hallmark of malignant tumors, can be monitored with a tracer and picked up on a PET scan.  In the case of a pancreas, injecting 2[18F]-fluoro-2-deoxy-D- glucose can be used to detect pancreatic cancer by looking where in the pancreas the highest concentration of the tracer exists (6).    

Introduction (continued)

Prior to this, pancreas PET scans were traced with 11C-labelled L methionine (6), which cannot differentiate between pancreatic cancer and chronic pancreatitis (inflammation of the pancreas due to digestive enzymes being activated, before they are secreted into the duodenum of the small intestine and start attacking the pancreas [13]).  In this study, the goal was to assess the performance of 2[18F]-fluoro-2-deoxy-D- glucose PET scans in being able to discern between pancreatic cancer and chronic pancreatitis.  In addition, the researchers wanted to see how much more accurate PET scans were than CAT scans.  



Methods

Eighty patients, who were going to have pancreatic surgery, entered the prospective trial.  Next, they were divided into four test groups.  Group I consisted of 42 patients that had confirmed pancreatic ductal cancer, group II consisted of six patients with periampullary cancer (a type of cancer that involves the ducts that connect between the liver and pancreas and where they join with the small intestine [11]), group III had 32 patients with chronic pancreatitis, and Group 4 consisted of the normal controls, which had 10 patients without pancreatic cancer or chronic pancreatitis.    They were all administered a preoperative dose of 250-350 mBq of 2[18F]-fluoro-2-deoxy-D- glucose.  This was administered intravenously and these patients were scanned 45 minutes later.  Intensity displays of the tracer in the pancreatic region were taken during the scan to show the presence of pancreatic cancer.  Next, the presence of pancreatic cancer was confirmed using biopsies of the pancreas to be compared to the PET scan results.  

Results/ Discussion 

Image Above: PET scan of a pancreas of a patient with pancreatic cancer.

From these patients, high resolution 2[18F]-fluoro-2-deoxy-D- glucose PET scan images were taken of the upper abdomen (6).  Since normal pancreas glucose utilization is very low, it provided an easy background to compare, where the tracer was going and if it was related to an increase in glucose metabolism (increased glycolysis is a hallmark of cancer).  Additionally, one thing the researchers mentioned was using furosemide (a water pill that can be used to reduce fluid retention and swelling [7]) in conjunction with the PET scan, which can reduce the 2[18F]-fluoro-2-deoxy-D- glucose retention that can occur in the urinary system.  If this retention is avoided it can provide a clearer PET scan (6).  


The researchers found that in patient group I, 41 of 42 patients had vastly increased 2[18F]-fluoro-2-deoxy-D- glucose uptake.  In these patients, the median uptake of the tracer (2[18F]-fluoro-2-deoxy-D- glucose) was 3.09 and the PET scan had a sensitivity of 98% detection.  All patients that exhibited stage III and IV pancreatic cancer in the test groups had an increased uptake of 2[18F]-fluoro-2-deoxy-D- glucose in their PET scans.  In five of eight patients that had stage I and II pancreatic cancer, there was not an increased uptake of 2[18F]-fluoro-2-deoxy-D- glucose on their PET scans.  A confirmation that the PET scan worked well with the tracer was that 28 of 32 chronic pancreatitis patients did not have a pancreas that was visualized by the PET scan.  The standard median uptake of the tracer was only 0.87 for these individuals with a detection rate for the PET scan of 88%.  Using a p- test, these researchers confirmed that the uptake value on group I (pancreatic cancer) and group II (periampullary carcinoma) was indeed significantly different compared to that of group III (chronic pancreatitis) (6).          


One final test the experimenters were looking at was the accuracy of a CAT scan versus a PET scan. The researchers found that only three patient's tumors of eight had suspicious masses that were detected by a CAT scan (38% detection rate).  PET scans had a significantly higher sensitivity detection for pancreatic cancer than CAT scans using an X^2 analysis (p<0.01).  In addition, PET scans proved they were also the better alternative to detecting pancreatic cancer versus chronic pancreatitis (6).  


Analysis


1) What are the differences between a CAT scan and a PET scan?
A positron emission tomography scan, known as, a PET scan uses a radioactive substance called a tracer to look for a disease in the body and present this via an image.  A PET scan is great for looking at cancer because it shows how tissues and organs are working and if they are working properly (4). A CAT scan is a Computed axial tomography scan, which uses X- rays to make a picture of the structures inside a body.  During a CAT scan, the scanner will send many X- rays, through the portion of the area being studied.  With each of these X- rays a thin slice of the organ or area being studied is made.  In most cases, an iodine dye is also inserted to make visualization of the organs or areas being studied easier to visualize on the scans.  In addition, the dye can be used to check blood flow to the area, and see tumors (3).       


2) If we are inserting a radioactive substance into a person can that increase their incidence of cancer?
The radioactive substances that are inserted as tracers in PET scans, usually do not increase the risk of a person to get cancer, due to the half life being extremely short (Class notes).  2[18F]-fluoro-2-deoxy-D- glucose has a half life of 110 minutes, or just under 2 hours (5).   


3)  Relevance of this paper and do we by the data.
One thing to mention about this study was it was performed in 1992 and 1993.  It was posted in 1995. Based on how quick data in cancer studies and trials change it is likely out of date.  In addition, this can be seen by the non-color PET scan pictures, included in the paper (6).  In addition, to this paper being out of date, it appears PET scans used currently are only used for pancreatic cancer in identifying how far the cancer has metastasized (12) and not in the sole detection of pancreatic cancer (as per searching on Google and I could not find anything that suggests this research was furthered and was used to detect pancreatic cancer).  As for if the data is believeable, I would say it is.  The researchers provided the statistical tests for the data and it was significantly different.  This type of research has also been replicated.  A replicate of this experiment was done by British doctors and researchers. They ran a test to see if 2[18F]-fluoro-2-deoxy-D- glucose PET scans could be used to differentiate between chronic pancreatitis and pancreatic cancer (8) (an almost identical experiment to the journal article this blog post was done on).  Their methods were also set up very similar with test subjects consisting of: pancreatic cancer patients, chronic pancreatitis patients, and a group of control patients (8).  However, one difference they included in their test group were patients with acute pancreatitis (8).  Their conclusion was the same,as the journal article presented in the blog post: 2[18F]-fluoro-2-deoxy-D- glucose PET scans are an imperative non-invasive method for distinguishing between chronic pancreatitis and pancreatic cancer (8).  The researchers also added that using PET scans can be extremely helpful in diagnosing patients preoperatively, if they have unknown pancreatic masses (8).  


4) Relating this article back to an older post.  
My last blog post consisted of researchers identifying genes that were affected by pancreatic cancer that lead to an altered glucose metabolism (10) (however, one additional thing to keep in mind is their test was ran on myoblasts and not pancreatic cells.  This altered glucose metabolism is involved in reduced glycogen synthesis and also an increase in the accumulation of ATP and NADH (can be reviewed here for more info [10]).  In this paper, the researchers also found that pancreatic cancer led to an increase in lactate production and induced proteolysis.  After reading about how PET scans work using a tracer, I wonder if one day or in the very near future, the doctors could use a tracer that could detect the increased lactate production in the pancreas (instead of using a glucose tracer), which could signify an individual has pancreatic cancer.  Using this lactate tracer would also lead to a higher confirmation rate of cancer because in my last blog post (the experiment was ran in or near 2004, much later than this current paper being discussed in this blog post) the experiment showed that pancreatic cancer had a confirmed increase in lactate production.  As of right now, doctors can already test if there is high levels of lactate in the blood, which could make it even easier to synthesize some sort of lactate tracer (9).  One problem that could arise form using a lactate tracer is other parts of the body would light up very highly.  Another problem that could arise is high levels of lactate in certain areas of the body can mean a variety of other diseases exists, such as, sepsis, heart attack, congestive heart failure, severe lung disease, pulmonary edema, etc (9).  The feasibility of using a lactate tracer, unfortunately, is likely not an option.  In addition, after realizing how tracers work, using one for identifying pancreatic cancer would be exceedingly difficult, as it would be hard to find something very distinct to pancreatic cancer and something that is not found elsewhere in the body.  Maybe a better approach would be genetic testing and finding a distinct gene that is over- or under- expressed (finding out about if this is possible will have to be saved for another blog post).  


Final Comments


Overall, This journal article fit very nicely in class, as we are just beginning to discuss therapies and diagnosing of cancer.  PET scans along with CAT scans and MRI's are all techniques doctors use to assist them in identifying and viewing the progress of cancer in the body.  Even though this journal article could lead to great breakthroughs in beating pancreatic cancer, once again doctors are stopped in their tracks due to the commonalities of the many symptoms of pancreatic cancer.  As of right now, there is not a single known symptom to pancreatic cancer that is specific to only pancreatic cancer. Unfortunately, many symptoms known [to pancreatic cancer] can be related to a plethora of other diseases.


Thanks for reading!
--Quincy


Quick link to paper: http://gut.bmj.com/content/36/5/771.full.pdf 

Citations

1) Arnoux et al. Orphanet Journal of Rare Diseases 2011 6:63

2) Basso, D. "Altered Glucose Metabolism and Proteolysis in Pancreatic Cancer Cell Conditioned Myoblasts: Searching for a Gene Expression Pattern with a Microarray Analysis of 5000 Skeletal Muscle Genes." Altered Glucose Metabolism and Proteolysis in Pancreatic Cancer Cell Conditioned Myoblasts: Searching for a Gene Expression Pattern with a Microarray Analysis of 5000 Skeletal Muscle Genes. GUT: An International Journal of Gastroenterology and Hepatology, 03 Feb. 2004. Web. 30 Apr. 2012.<http://gut.bmj.com/content/53/8/1159.full>.

3) "CAT Scan (Computed Tomography or CT Scan): Procedure, Preparation, and Results." WebMD. 12 May 2010. Web. 15 May 2012. <http://www.webmd.com/a-to-z-guides/computed-tomography-ct-scan-of-the-body>.

4) Dugdale, David C. "PET Scan." Medline Plus. U.S. National Library of Medicine, 21 Nov. 2010. Web. 15 May 2012. <http://www.nlm.nih.gov/medlineplus/ency/article/003827.htm>.

5) "Fact Sheet: Fludeoxyglucose [18F]." Cyclotron. Web. 15 May 2012. <http://www.cyclotron.nl/library/resource/file/pdf/fs_web/cyclo_fs_fludeoxyglucose.pdf>.

6) Friess, H., J. Langhans, M. Ebert, H. G. Beger, J. Stollfuss, S. N. Reske, and M. W. Buchler. "Diagnosisofpancreaticcancerby 2[18F]-fluoro-2-deoxy-D-glucosepositron Emissiontomography." GUT: An International Journal of Gastroenterology and Hepatology 36 (1995): 771-77. Group.bmj.com. Web. 14 May 2012. <http://gut.bmj.com/content/36/5/771.full.pdf>.

7) "Furosemide." PubMed Health. U.S. National Library of Medicine, 1 Sept. 2010. Web. 15 May 2012. <http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0000791/>.

8) Imdahl, A., Nitzsche, E., Krautmann, F., Högerle, S., Boos, S., Einert, A., Sontheimer, J. and Farthmann, E. H. (1999), Evaluation of positron emission tomography with 2-[¹⁸F]fluoro-2-deoxy-D-glucose for the differentiation of chronic pancreatitis and pancreatic cancer. Br J Surg, 86: 194–199. doi: 10.1046/j.1365-2168.1999.01016.x

9) "Lactate: The Test." Lab Tests Online. Web. 16 May 2012. <http://labtestsonline.org/understanding/analytes/lactate/tab/test>.

10) Mehta, Quincy. "Pancreatic Cancer Alters Glucose Metabolism." Cancer Biology. 3 May 2012. Web. 16 May 2012. <http://islaslab.blogspot.com/2012/05/pancreatic-cancer-alters-glucose.html>.

11) Mehta, Vivek K. "Ampullary Carcinoma ." Medscape Reference. 13 Jan. 2012. Web. 16 May 2012. <http://emedicine.medscape.com/article/276413-overview>.

12) "Pancreatic Cancer Diagnosis and Early Detection." WebMD. 2012. Web. 16 May 2012. <http://www.webmd.com/cancer/pancreatic-cancer/pancreatic-cancer-diagnosis>.

13) WebMD. "What Is Pancreatitis?" WebMD. Web. 15 May 2012. <http://www.webmd.com/digestive-disorders/digestive-diseases-pancreatitis>.