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Description
A review of Cholangiocarcinoma and Nuclear medicine image findings.
Document Sample
Monitoring Cholangiocarcinoma
with F18-FDG PET/CT imaging.
Mike Durkan
OIT Winter Term 2009
Nuclear Medicine Externship Case Study
Contents
Introduction---------------------------------------- 3
F18 FDG---------------------------------------------- 4
PET/CT Procedure--------------------------------- 5-9
Cholangiocarcinoma------------------------------10-13
FDG PET and CCC----------------------------------14-18
NOPR-------------------------------------------------19
NOPR: Proposed Coverage----------------------20
Conclusion------------------------------------------21
References------------------------------------------22
Introduction
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
Cholangiocarcinoma.
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
MATERIALS
• 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
EQUIPMENT
• 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
configuration
• 6 or more table positions.
PET/CT Procedure
PATIENT PREPARATION
• Fasting for 6-8 hours prior
• Physical activity is restricted
• Meals low in carbohydrates and high in protein and lipids are
recommended.
– 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
Diabetes.
– 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
paper.
– 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
INJECTION
• 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
ACQUISITION & PROCESSING
• 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
• 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
population.
• Unknown etiology. Some conditions are
suspected to increase a person’s risk of
developing CCC. Research shows a correlation
between Primary Sclerosing Cholangitis (PSC).
Cholangiocarcinoma
• Perhilar CCC, Klatskin tumor and
Peripheral CCC, are commonly found
at the bifurcation of the Left and
Right Hepatic bile ducts
(extrahepatic).
• 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
histiologically.
• Perihilar is easier to identify with CT,
MRI, and ERCP (Endoscopic
Retrograde
Cholangipancreatography). CT is also
used to monitor the tumor’s mass
over time
Cholangiocarcinoma
Bismuth-Corlette
STAGING
• Oncologists commonly use the American Joint
Committee on Cancer Guidelines (AJCC) tumor, node,
and metastasis (TNM) scale to classify tumor
pathology.
• Surgeons use the Bismuth-Corlette classification to
further evaluate tumor resectability and required
procedures.
• 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
involvement.
• Treatment options usually consist of tumor resection,
however most tumors are desmoplastic formations
around the hilum and unresectable at diagnoses
Cholangiocarcinoma
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
F18-FDG.
• 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
CCC.
• 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
IMAGE ARTIFACTS
• 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
CCC.
• 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
accumulation.
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
accumulation.
• 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
grams/ml.
• The SUV value was correlated
with previous mediastinal
lymphnode values recorded in
October to rule out benign
activity.
• 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
SuperiorInferior. Notice the FDG uptake in the central part of the liver
RT LT
NOPR
• 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
coverage.
Proposed NOPR PET/CT Medicare Reimbursement Coverage
*CED: Coverage with Evidence Development
Conclusion
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.
References
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.
Hillner, Bruce E., Siegel, Barry A., & Liu, Dawei (2008). Relationship Between Cancer Type and Impactof
PET and PET/CT on Intended Management:Findings of the National Oncologic PET Registry. Journal of
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ofcholangiocarcinoma: consensus document. British Journal of Medicine, 51, Retrieved March 2,
2009, from http://gut.bmj.com/cgi/content/full/51/suppl_6/vi1.
Darwin, Peter E. (2008). Cholangiocarcinoma. In EMedicine [Web]. Medscape. Retrieved March 2, 2009,
from http://emedicine.medscape.com/article/277393-overview
Reihnhart, M. J., Strunk, H., & Gerhart, t. (2005). Detection of Klatskin’s Tumor in Extrahepatic Bile Duct
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