Cholangiocarcinoma imaged with F18 FDG by MikeDurkan

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									Monitoring Cholangiocarcinoma
with F18-FDG PET/CT imaging.
                Mike Durkan
            OIT Winter Term 2009
    Nuclear Medicine Externship Case Study
Introduction---------------------------------------- 3
F18 FDG---------------------------------------------- 4
PET/CT Procedure--------------------------------- 5-9
FDG PET and CCC----------------------------------14-18
NOPR: Proposed Coverage----------------------20
       In 2005 under Medicare’s Coverage with Evidence (CED) program the National
Oncologic PET Registry was created. “The NOPR is a collaboration of the American
College of Radiology Imaging Network (ACRIN), the American College of Radiology
(ACR), and the Academy of Molecular Imaging (AMI), to ensure access to Medicare
reimbursement for certain types of positron emission tomography (PET) scans.” The
creation of the NOPR allows future reimbursement options to be developed from
evidence based data and research. Recently , on January 6, 2009, a group of
physicians submitted a 24 page memorandum that proposed a changed in current
Medicare reimbursement coverage for FDG PET oncological indications.
       The change would make FDG PET a stronger tool in the management of cancer.
With this change new cancers and new coverage options would expand the
diagnostic use of FDG PET. One cancer with proposed changes in coverage was
       On January 19th, 2009, I performed a PET/CT study on a 44yr old female that
had a history of Klatskins tumor a Perihilar Cholangiocarcinoma. Due to the
pathophysiological nature of this cancer and level of tumor growth, surgical resection
was unable to completely remove the tumor. Malignant cells still remained in the
biliary tract and surrounding tissue. To further evaluate the level of malignant tumor
growth and assess treatment options the oncologist used PET/CT imaging.
       This case study will describe the FDG PET/CT procedure, the pathophysiology of
Cholangiocarcinoma, and how FDG PET/CT benefits patients with this disease.
                                F18 FDG
• F18 FDG (flurodeoxyglucose) is a nonorganic           F18 FDG
  analog of the organic molecule glucose.
• F18 is produced via duetron bombardment of
  Neon-20 or proton bombardment (p,n) of
  Oxygen-18 in a medical cyclotron. (the latter is
  most often used).
    – T1/2= 110 minutes
    – The annihilation of positronium (a positron and
      electron) produces two 511 keV photons that
      travel 180° degrees apart.
    – F18’s mean positron range is 0.2mm with a         Glucose
      maximum range of 2.4mm. This is an ideal range
      for PET resolution.
• F18 FDG is actively transported through
  cellular membranes where the enzyme
  hexokinase transforms the molecule into FDG-
  6-phosphate. Once FDG-6-P is produced in the
  first step of glycolysis, the molecule
  permanently remains in the cellular cytosol.
                        PET/CT Procedure
•   1x Butterfly needle.
•   1x Three way stopcock
•   2x 10cc syringe w/saline (15%NaCl
    in 10ml sterile H₂O)
•   1x Tungsten PETPig™
     – 21mm (7 half value layers)
• 20oz solution of 50%H₂O and 50%
  Barium oral CT contrast
• 1x Positive pressure cap
                   PET/CT Procedure
• GE Discovery ST PET/CT scanner.
• Xeleris Hawkeye PET/CT
  processing module
• Bismuth germanate (BGO)
  scintillation crystal.
   – BGO cut-block detector
   – 7.1gm/cm³
   – 300nsec Decay time
• 2D tungsten detector
• 6 or more table positions.
                    PET/CT Procedure
• Fasting for 6-8 hours prior
• Physical activity is restricted
• Meals low in carbohydrates and high in protein and lipids are
    – To reduce cardiac FDG uptake, Doctors want the heart to be processing fats
      into energy.
• Blood Glucose levels are taken from patients with Type I and II
    – Patients with Type I or Diabetes Mellitus continue normal management of
      Blood glucose levels.
• Prior studies and Patient histories are brought either on film, CD, or
    – Most patients are referred from Fairbanks, Nome, and other regions in
      Alaska. The Radiologists need a firm patient history and comparative image
      studies to evaluate prior, initial, and future diagnostic imaging.
                  PET/CT Procedure
• Blood Glucose levels are checked only if the patient recently ate or the
  patient has diabetes.
• Patient anxiety and claustrophobic issues are allayed by administering
  0.5mg aprazolam (Xanax) one hour before imaging. Patient transportation
  after the study must be supplied by a significant other or taxi service
• IV access is established with a Butterfly and Three way stopcock.
• The F18 FDG dose is then assayed and brought into the room.
• A small volume of saline is flushed through the IV to ensure patency.
• The dose is injected and followed by 20 cc Saline.
• The patient’s 1 meter radiation dose rate is about 1mrem/hr so the patient
  remains in the lead shielded injection room for 45 minutes to 1 hour.
• To reduce brown fat uptake, warm blankets are supplied and the room’s
  temperature is kept warm.
                         PET/CT Procedure
•   The patient is positioned supine, head first with their arms above their head.
•   Metallic objects, false-teeth, and prostheses are removed from the field of view.
•   The CT consists of an 8 slice 25 second scan from the orbitomeateal line through the
    pelvis. The average table length is 75cm. Sometimes scan length is extended to
    accommodate taller patients.
•   2D PET acquisition allows for less computer processing and larger camera bores to
    prevent claustrophobia.
•   The PET acquisition averages 24 minutes with 6 bed stations.
•   Lung specific PET/CT studies are acquired after limited whole body scans to better
    differentiate Lung parenchyma and changes in FDG localization.
     –   Some lung cancers, especially non-small cell carcinoma, accumulate FDG over time.
•   After acquisition the images are assessed for motion and attenuation accuracy.
•   Before the data is displayed the computer automatically applies an MLEM and OSEM
    HANN reconstruction algorithm.
•   The RAW PET/CT data is sent to the Advantage DICOM 4.3 workstation where the fused
    data is displayed in the sagittal, transverse, coronal planes.
•   The DICOM 4.3 and Dr. Xeleris workstation allows Radiologists to use quantitative image
    analysis with Body weight and Body surface area Standard uptake values (SUV).
• Cholangiocarcinoma (CCC) has two
  subtypes with ancillary groupings:
   – Perihilar: (70-85%)Most common form of
     cholangiocarcinoma that is usually a highly
     desmoplastic (fibrous) adenocarcinoma.
       • Peripheral
       • Hilar (Klatskins tumor)
   – Intrahepatic: (20-25%) This form usually grows
     as a mass around the biliary tract in the liver
• 1/100,000 chance of developing CCC.
• 6 month survival rate for overall patient
• Unknown etiology. Some conditions are
  suspected to increase a person’s risk of
  developing CCC. Research shows a correlation
  between Primary Sclerosing Cholangitis (PSC).
•   Perhilar CCC, Klatskin tumor and
    Peripheral CCC, are commonly found
    at the bifurcation of the Left and
    Right Hepatic bile ducts
•   Perihilar CCC also develops in the
    intrahepatic bile ducts.
•   The desmoplastic nature causes the
    cancer to be mistaken for other
    cancers (HCC, pancreatic cancer
    metastases, and gallbladder cancer).
•   Perihilar and Intrahepatic CCC are
    diametrically different; gentically and
•   Perihilar is easier to identify with CT,
    MRI, and ERCP (Endoscopic
    Cholangipancreatography). CT is also
    used to monitor the tumor’s mass
    over time
•   Oncologists commonly use the American Joint
    Committee on Cancer Guidelines (AJCC) tumor, node,
    and metastasis (TNM) scale to classify tumor
•   Surgeons use the Bismuth-Corlette classification to
    further evaluate tumor resectability and required
•   Physiologically, Perihilar and Intrahepatic CCC present
    with conspicuous symptoms. Physical symptoms often
    present in late stages of tumor growth.
•   50% of patients have lymph node involvement at initial
    diagnosis (Stage III). 10-20% have peritoneal
•   Treatment options usually consist of tumor resection,
    however most tumors are desmoplastic formations
    around the hilum and unresectable at diagnoses
Diagnostic Approach for Cholangiocarcinoma

                      MR and CT imaging

                                PET Scan
                      FDG PET and CCC
• Medicare's establishment of the NOPR allowed new cancers to be imaged with
• CCC was one of the cancers the NOPR provided CED reimbursement for.
• This platform allowed physicians to research the impact of FDG PET imaging in
• One article claimed FDG F18 imaging was 92% sensitive and 93% specific for
  detecting CCC. This finding includes Perihilar and Intrahepatic CCC.
• No research has been done on the diagnostic significance of FDG F18 imaging to
  prevent CCC. Current studies have been developed around staging, treatment
  options, and monitoring CCC.
• Compared to MRI, ERCP, CT, and US; FDG PET imaging is more sensitive in
  identifying distant metastases in CCC and can differentiate between Primary
  Sclerosing Cholangitis (PSC), a benign condition of the biliary system. CCC and
  PSC are structurally similar and can be mistaken for each other.
                              FDG PET and CCC
•   According to the Bismuth-Corlette
    classification scheme for Klatskin CCC
    adenocarcinomas, patients with Type I-IV
    receive a hepaticojejunostomy (biliary
    stent). Some FDG PET studies show false
    uptake from these structures making it
    difficult to discriminate between tumor
    uptake and biliary stent uptake.
     –   The patient imaged had a known plastic biliary
         stent that showed little FDG activity compared
         to tumor activity.
•   Kluge et al. suggests normal SUV
    quantitative values may produce inaccurate
    grading of tumor activity. The semi
    quantitative T/N (tumor/non-tumor) grading
    scales are better for FDG PET imaging in
•   Tumor size may limit FDG accumulation and
    produce a false negative in early detection.
•   Cholangitis and inflammation from other
    hepatobiliary diseases that commonly occur
    comorbidly with CCC can produce false FDG
                         FDG PET and CCC
•   The patient imaged on January 19th had a
    previous PET/CT study in October ‘08. The     October SUV=3.5 grams/ml.
    FDG PET studies were used to monitor
    Klatskin tumor growth.
•   According to the TNM grading scale the
    patient had stage III CCC and was treated
    with a variety of procedures.
•   The patient underwent tumor resection and
    other major surgical interventions to
    remove the tumor. The Bismuth-Corlette
    scheme showed a Type IV tumor.
•   Following experimental treatment with
    Xeloda, a chemotherapy drug, the patient’s
    cancer was restaged with a PET/CT and
    Abdomen CT.
•   Three non-enlarged lymphnodes in the
    mediastinum showed increased FDG
•   The Radiologist used Qualitative
    comparisons with Standard Uptake Values
    for patient weight. SUVs greater than 2.5-3
    grams/ml are considered abnormal.             January SUV=5.7 grams/ml.
                    FDG PET and CCC
• The January ‘09 image shows two        January ’09: PET Fused with
  non-enlarged mediastinal               Mediastinal Lymphnode metastases
  lymphnodes with increased activity
  with a maximum SUV of 4.6
   • The SUV value was correlated
       with previous mediastinal
       lymphnode values recorded in
       October to rule out benign
• The Second image shows the initial
  diagnoses of Klatskins tumor with an
  Abdomen Pelvis CT study performed
  in 2005.
   • The patient’s physical symptoms,
       liver enzyme labs, and other
       antigen specific blood tests
       further indicated CCC.
   • The tumor’s location and growth
       indicated a CCC Klatskin tumor.
                                         September ’05: CT showing
                                         initial Klatskins tumor
                     FDG PET and CCC
January ‘09: This image set shows fused PET/CT transverse 8.82mm slices from
SuperiorInferior. Notice the FDG uptake in the central part of the liver

RT            LT
• The National Oncologic PET Registry (NOPR) allows
  patients to receive free diagnostic testing for national
  research purposes.
• With the data collected over that last four years and
  current proposals for Medicare reimbursement changes,
  FDG PET imaging will allow more accurate diagnostic
  data to the management of cancer.
• The management of CCC is just one cancer that has been
  shown to benefit from FDG PET imaging.
• Later this month the Medicare Evidence Development &
  Coverage Advisory Committee (MedCAD) will release its
  finial decision regarding the proposed changes.
   – Following this slide is a list of proposed changes from current
       Proposed NOPR PET/CT Medicare Reimbursement Coverage

*CED: Coverage with Evidence Development
     The main purpose of this case study was to show how
FDG PET imaging can benefit the management of cancer,
specifically CCC. Without utilization of this technology and
established databases like the NOPR, management of CCC in
the mentioned patient’s care may have been limited or
demanding. Although FDG PET in CCC management is a
narrow example of NOPR data collection, this shows the level
of opportunities offered through this organization and the
discernment used to find newer more advanced non-invasive
procedures. Over time, as more NOPR CED studies are
submitted and more data is collected, coverage entities may
provide broader plans to compensate for changes in FDG PET
imaging in the management of disease.
Hillner, Bruce E., Siegel, Barry A., Liu, Dawei, & Shields, Anthony F. (2008). Impact of Positron Emission
     Tomography/Computed Tomography and Positron Emission Tomography (PET) Alone on Expected
     Management of Patients With Cancer: Initial Results From the National Oncologic PET Registry.
     Journal of Clinical Oncology, 26, 1155-1161.
Kieding, Susanne, Hansen, Soren B., & Rasmussen, Henrick H. (1998). Detection of Cholangiocarcinoma
    in Primary Sclerosing Cholangitis by Positron Emission Tomography. Hepatology. 28, 700-706.
Kluge, Regine, Schmidt, Frank, & Caca, Karel (2001). Positron Emission Tomography With [18F]Fluoro-2-
    deoxy-D-glucose for Diagnosis and Staging of Bile Duct Cancer. Hepatology. 33, 1029-1035.
Gores, Gregory J. (2003).Cholangiocarcinoma: Current Concepts and Insights. Hepatology. 37, 961-969.
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     PET and PET/CT on Intended Management:Findings of the National Oncologic PET Registry. Journal of
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Bismuth, Henri (1992).Management Strategies in Resectionfor Hilar Cholangiocarcinoma. Annual Journal
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Khan, S. A., Davidson, B. R., & Goldin, R Guidelines for the diagnosis and treatment
   ofcholangiocarcinoma: consensus document. British Journal of Medicine, 51, Retrieved March 2,
   2009, from
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Reihnhart, M. J., Strunk, H., & Gerhart, t. (2005). Detection of Klatskin’s Tumor in Extrahepatic Bile Duct
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