| [Objective]1. To assess the value of PET/CT in the diagnosis of hepatiocellular carcinoma.2. To assess the value of PET/CT in the diagnosis of intrahepatic cholangiocarcinoma.3. To evaluate the identify value of PET/CT in diagnosing hepatocellular carcinoma and intrahepatic cholangiocarcinoma by means of analyzing PET/CT imaging findings and clinical data.[Materials and Methods]1. Study objective1.1 Control group30 healthy subjects were selected as a control group who underwent 18F-FDG PET/CT in Nanfang PET centre, Nanfang Hospital in June,2010. The clinical examination, X-Rays, B-ultrasound and serum tumor markers of all of 30 healthy subjects were normal.1.2 hepatocellular carcinoma patient groups91 patients with clinical diagosis of hepatocellular carcinoma were enrolled in this study including 83 men and 8 women, aged from 30 to 84 years old, with a mean age of 52.0 years old.56.0%(51/91) of patients with liver cirrhosis,90.1% (82/91) of patients with patients with hepatitis B or hepatitis C,96.7 (88/91) of patients check AFP,74.7%of (68/91) of patients check CEA,74.7%of (68/91) of patients check CA199. All of patients underwent whole body 18F-FDG PET/CT scan and tumor maker examination. At the same time,83 patients underwent contrast enhancement CT in upper abdomen.All the patients were diagnosed by the histopathology examination with the sample obtained by operation or puncture biopsy.1.3 intrahepatic cholangiocarcinoma patient groups45 patients with clinical diagosis of intrahepatic cholangiocarcinoma were enrolled in this study including 27 men and 18 women, aged from 23 to 76 years old, with a mean age of 55.0 years old.13.3%(6/45) of patients with liver cirrhosis, 37.8%(17/45) of patients with patients with hepatitis B or hepatitis C,91.1%(41/45) of patients check AFP,84.4%(38/45) of patients check CEA,88.9%(40/45) of patients check CA199. All of patients underwent whole body 18F-FDG PET/CT scan and tumor maker examination. At the same time,40 patients underwent contrast enhancement CT in upper abdomen. All the patients were diagnosed by the histopathology examination with the sample obtained by operation or puncture biopsy.2. Main equipments and imaging agentThe examinations were carried out using a GE Discovery LS PET/CT scanner (GE, Healthcare, and Waukesha, WI). The positron emitter was produced using the cyclotron of PET tracer (GE, Healthcare, Waukesha, WI).The tracer 18F-FDG, was manufactured automated by the tracer synthesis system of FDG Microlab (GE, Healthcare, Waukesha, WI), with a radiochemical purity> 95%.3. Imaging methods and conditions All patients and healthy Subjects underwent PET/CT scans after fasting at least 6 hours prior to examination. Patients also received orally 600ml and 200ml of 1.5% diatrizoate meglumine at an hour and 5 minute before the scans.5.5MBq/kg of i8F-FDG was then administrated intravenously via a T tube. After about 60 minutes of relaxed rest in a supine position in dark rooms without visual or acoustic stimulations, the patients were asked to void and were then placed into the PET/CT scanner for image acquisition. The image acquisition included non-enhanced CT scan and PET scan covered the range from the head to the middle thigh (6-8 bed position). CT scan was performed initially with a voltage of 140 kV, a current intensity of 160 mA, and 0.8-second tube rotation, and 5-mm section thickness. After CT scan finished, the scanner was repositioned to the landmark position and PET scan was then acquired with 4 min/bed position. Delayed scan was performed in the patients who needed to exclude the influence of the physiological uptake in the gastrointestinal tract。4. Image reconstruction and fusionPET images were reconstructed by using a standard iterative algorithm (ordered subset expectation maximization) with CT data being used for attenuation correction. The CT images were reconstructed by using a standard method.The thickness of each slice of PET and CT after reconstruction was 4.25mm. The acquired images of PET and CT were sent to the Xeleris (GE Medical Systems) workstation for image registration and fusion.5. Image analysis and Diagnostic CriteriaPET images,CT images and PET/CT images were interpreted independently by two experienced senior physicians of nuclear medicine and two experienced senior physicians of CT diagnosis. The focus dense higher than surrounding normal tissue was defined as high uptake. The maximum standardized uptake value (SUVmax) was calculated automatically by the workstation by setting the regions of interest (ROI) on the lesion.The diagnosis of primary liver cancer by PET/CT based on the following criteria:Primarily Tumor:exclude liver metastatic tumor,the wall of the intestine with the most intense 18F-FDG uptake was considerd primary cancer. Portal tumor thrombus:if portal vein increased thick and increased 18F-FDG uptake was seen in the same region on PET, the diagnosis of portal tumor thrombus was established.Region lymph nodes and metastasis:exclude the physiological uptake, the intense 18F-FDG nodosity or massive uptake was considered metastasis. If the obviously morphological abnormality in lung on CT met the criteria of CT for diagnosing lung carcinomatosis, the diagnosis of lung carcinomatosis was established by CT even when no increased F-FDG uptake was seen in the same region on PET. The diagnosis of primary liver cancer by PET/CT combined with contrast enhancement CT based on the following criteria:either was masccline,we diagnosed praimay liver cancer,neither were masccline,we diagnosed benign lesions.6. Semi-quantitative AnalysisLesion with abnormal 18F-FDG uptake was identified by two experienced senior physicians of PET/CT. The maximum standardized uptake value (SUVmax) was calculated automatically by the workstation by setting the regions of interest (ROI) on the lesion. ROI was set and drawn according the following protocols:①ROIs were drawn in the liver lesions with the most intense 18F-FDG uptake.②if the obviously morphological abnormality liver on CT was not F-FDG avid, ROIs were drawn on the areas with visible morphological abnormality and then copied to the same region on PET. For the semiquantitative analysis, the size of ROIs was set at 4×4 pixels.7. Statistical analysis Statistical Package for the Social Sciences (SPSS) 13.0 (SPSS Inc., Chicago, IL) was used for statistical analysis. SUVmax was expressed as mean±standard deviation (X±S). The two independent samples byχ2 test was performed for statistical comparison of two independent samples of the positive rates in sensitivity,AFP,CEA a,CA199,hepatitis incidence,cirrhosis incidence,pathogenesis parts and lesions. The independent-sample t-test was performed for statistical comparison of two independent samples of SUVmax. The two independent samples byχ2 test was performed for statistical comparison of two independent samples of bile extension,portal tumor thrombus,region lymph nodes and distant metastasis.P<0.05 was considered statistically significant.[Results]1. Normal PET/CT studyA good understanding of the normal physiologic uptake in the whole body is important. It is a useful way to survey the lesions on PET/CT by comparing the different uptake of right side with that of left one in each of the section images. The brain is an organ with high 18F-FDG uptake due to marked glucose utilization, particularly in gray matter.18F-FDG is cleared primarily through the renal system, so the radioactivity in the urine, in the renal calices, ureters and bladder is very high. There is a mild generalized uptake in the liver, bone marrow and spleen. Normal variant uptake in the heart and bowel can also be seen. 18F-FDG uptake in the mesentery, greater omentum and other peritoneum is too low to be ignored. No morphological abnormality in peritoneum can be seen on CT images.2. hepatocellular carcinoma patient groups2.1 The primary tumor65 cases of hepatocellular carcinoma were located in right lobe,11 cases in left lobe,SUVmax was 5.81±3.89,including 31 cases of PET/CT imaging was low 18F-FDG uptake. The sensitivity of PET/CT for diagnosing primary lesions of hepatocellular carcinoma was 65.9%. At the same time,80 patients underwent contrast enhancement CT in upper abdomen. Contrast enhancement CT diagnosed accurately in 80 patients with malignant and in 3 patients with benign. The sensitivity of contrast enhancement CT for diagnosing primary lesions of hepatocellular carcinoma was 96.4%.The sensitivity of contrast enhancement CT is higher than PET/CT (χ2=25.602, P=0.000)2.2 Portal tumor thrombusPET/CT diagnosed accurately with portal tumor thrombus in 25 patients of hepatocellular carcinoma group.The false-positive diagnosis occurred in 1 patients with portal tumor thrombus and the false-negative diagnosis occurred in 1 patients with portal tumor thrombus. The sensitivity, specificity and accuracy of PET/CT were 96.4%,98.5% and 97.8%.2.3 Regional lymph node metastasisPET/CT diagnosed accurately with regional lymph node metastasis of hepatocellular carcinoma group in 5 patients,4 cases of PET/CT imaging was high 18F-FDG uptake. The false-positive diagnosis occurred in 1 patients with regional lymph node metastasis and the false-negative diagnosis occurred in 1 patients with regional lymph node metastasis. The sensitivity, specificity and accuracy of PET/CT were 100%,98.9% and 98.9%.2.4 Distant metastasis91 cases of hepatocellular carcinoma patients found 9 cases of distant metastasis, located mainly in lung and bone, all of cases PET/CT imaging was high 18F-FDG uptake. The sensitivity, specificity and accuracy of PET/CT were 100%,100% and 100%.3.intrahepatic cholangiocarcinoma patient groups 3.1 The primary tumor20 cases of intrahepatic cholangiocarcinoma were located in right lobe,15 cases in left lobe,SUVmax was 8.14±2.85,only 1 case of PET/CT imaging was low 18F-FDG uptake. The sensitivity of PET/CT for diagnosing primary lesions of intrahepatic cholangiocarcinoma was 97.8%.At the same time,40 patients underwent contrast enhancement CT in upper abdomen. Contrast enhancement CT diagnosed accurately in 32 patients with malignant and in 8 patients with benign. The sensitivity of contrast enhancement CT for diagnosing primary lesions of intrahepatic cholangiocarcinoma was 80.0%.The sensitivity of contrast enhancement CT is lower than PET/CT (χ2=7.070, P=0.008)3.2 Portal tumor thrombusPET/CT diagnosed accurately with portal tumor thrombus in 10 patients of intrahepatic cholangiocarcinoma group.The false-negative diagnosis occurred in 2 patients with portal tumor thrombus. The sensitivity, specificity and accuracy of PET/CT were 83.3%,100% and 95.6%.3.3 Regional lymph node metastasisPET/CT diagnosed accurately with regional lymph node metastasis of intrahepatic cholangiocarcinoma group in 21 patients,20 cases of PET/CT imaging was high 18F-FDG uptake. The false-positive diagnosis occurred in 1 patients with regional lymph node metastasis and the false-negative diagnosis occurred in 1 patients with regional lymph node metastasis. The sensitivity, specificity and accuracy of PET/CT were 100%,96.0% and 97.8%.3.4 Distant metastasis91 cases of intrahepatic cholangiocarcinoma patients found 25 cases of distant metastasis, one distant metastasis in omental of PET/CT imaging was low 18F-FDG uptake, all of cases PET/CT imaging was high 18F-FDG uptake. The sensitivity, specificity and accuracy of PET/CT were 96.0%,100% and 100%.4.The comparative research between hepatocellular carcinoma and intrahepatic cholangiocarcinoma(1)Imaging appearance of 18F-FDG PET/CT4.1 The primary tumor4.1.1 Lesions position and size65 cases of HCC located in right lobe,11 cases located in left,15 cases with diffused distribution (71.4% vs 12.1% vs 16.5%); 20 cases of intrahepatic cholangiocarcinoma were located in right lobe,15 cases in left lobe,10 cases with diffused distribution (44.4% vs 33.3% vs 22.2%)。Statistical differences between HCC and intrahepatic cholangiocarcinoma were showed on the location of the right lobe (χ2=9.354, P=0.002), and left lobe (x2=8.789, P=0.003), no statistical differences between HCC and intrahepatic cholangiocarcinoma with diffused distribution (χ2=0.661, P=0.416)For HCC,62 cases showed unifocal lesion,39 cases showed multiple lesions; For intrahepatic cholangiocarcinoma,30 cases showed unifocal lesion,15 cases showed multiple lesions,no statistical differences between HCC and intrahepatic cholangiocarcinoma were showed on lesion number, unifocal lesion were usual in both of them.Measure the maximum diameter of lesions,if there were multiple lesions,measure the maximum lesion; The maximum diameter of HCC is 6.90±4.85cm; The maximum diameter of intrahepatic cholangiocarcinoma is 6.90±4.85cm; the maximum diameter is bigger in HCC,but no statistical differences among groups (t=0.713, P=0.477)4.1.1.2 Metabolism of 18F-FDG between HCC and intrahepatic cholangiocarcinoma In 91 cases of HCC,60 cases were with abnormal 18F-FDG uptake,the positive rate is 65.9%. In 91 cases of intrahepatic cholangiocarcinoma,44 cases were with abnormal 18F-FDG uptake,the positive rate is 97.8%. Statistical differences among groups showed on positive rate (χ2=16.969, P=0.000)SUVmax of HCC and intrahepatic cholangiocarcinoma was 5.81±3.89 vs 8.14±2.85;the SUVmax of HCC is lower than intrahepatic cholangiocarcinoma (t=±3.565, P=0.001). SUVmax of abnormal lesions in HCC and intrahepatic cholangiocarcinoma was.59±3.65 vs 8.27±2.73,no statistical differences among groups (t±1.053, P=0.295)4.1.1.3 Lesions by cholangiectasis between HCC and intrahepatic cholangiocarcinoma7.6% lesions in HCC were accompanied with cholangiectasis,1 cases was complicated by hepatolithiasis.93.3% lesions in intrahepatic cholangiocarcinoma were accompanied with cholangiectasis.The incidence of cholangiectasis is significantly higher in intrahepatic cholangiocarcinoma (χ2=95.817, P=0.000)4.1.2 portal vein and branches or Vena cava tumor thrombus27.5% cases of HCC were accompanied with portal vein and branches or Vena cavatumor thrombus,.Only Vena cava was involved in 1 case, only portal vein and branches was involved in 20 cases,both portal vein and Vena cavatumor thrombus were involved in 4 cases.26.7% cases of intrahepatic cholangiocarcinoma were accompanied with portal vein and branches or Vena cavatumor thrombus,.Only portal vein and branches was involved in 11 cases,both portal vein and Vena cavatumor thrombus were involved in 1 cases.The incidence is higher in HCC,but no Statistical differences among groups showed on the incidence of portal vein and Vena cava tumor thrombus, (χ2=0.010, P=0.921)4.1.3 Lymph node metastasis Only 4.4% cases of HCC accompanied with lymph node metastasis,44.4% cases of intrahepatic cholangiocarcinoma accompanied with lymph node metastasis, the incidence of lymph node metastasis is significantly higher in intrahepatic cholangiocarcinoma than HCC (χ2=33.231, P=0.000).In HCC group, lymph node metastasis is respectively located on hepatic hilum, peritoneum region,mediastium. In intrahepatic cholangiocarcinoma group, lymph node metastasis is respectively located on hepatic hilum, lesser curvature,peritoneum region,the head of the pancreas,near by diaphragm,supraclavicular and infracclavicular fossa, neck,elbow,et al.9 cases only took palace in intraperitoneal region,and 2 cases only took place in extraperitoneal region (neck, supraclavicular fossa),10 cases took place in intraperitoneal and extraperitoneal region. In HCC group, lymph node metastasis is usually restricted in intraperitoneal region especially in hepatic hilum, peritoneum region,occasionally skip metastasis; In intrahepatic cholangiocarcinoma group,lymph node metastasis is usually wide range,usually had distant lymph node metastasis,especially in supraclavicular and infracclavicular fossa;In HCC group,there is no metastasis in supraclavicular and infracclavicular fossa.4.1.4 Distant metastasisIn HCC group,9.8% patients had distant metastasis; In intrahepatic cholangiocarcinoma group,55.6% had distant metastasis, The incidence of distant metastasis is significantly higher in intrahepatic cholangiocarcinoma group (χ2=33.488, P=0.000). In HCC group,the locations of distant metastasia are respectively 6 in bone,1 in lung,2 in bone and lung. In intrahepatic cholangiocarcinoma group,the locations of distant metastasia are respectively 13 in omentum majus,13 in mesentery,6 in capsulafibrosa,9 in bone,7 in lung,2 in adrenal gland,2 in muscle,1 in prostate.Distant metastasis is rarely in HCC group,mainly in lung and bone; Distant metastasis is more commonly in intrahepatic cholangiocarcinoma group,mainly in peritoneum(59.3%),bone ,lung, adrenal gland,muscle, and prostate.(2).Tumor markersIn HCC group,96.7% patients with elevated AFP, compared with 91.1% patients in intrahepatic cholangiocarcinoma group;74.7% patient with elevated CEA compared with 84.4% patients in intrahepatic cholangiocarcinoma group.74.7% patient with elevated CA199 compared with 88.9% patients in intrahepatic cholangiocarcinoma group.The positive of AFP is higher in HCC group (85.4% vs 42.2%,χ2=23.081, P=0.000).The AFP is respectively 6661.37±19956.24,198.80±758.16 in HCC and intrahepatic cholangiocarcinoma group,the increase of AFP is higher in HCC group (t=2.815, P=0.006).In HCC group, there is only 2.9% patient showed positive in CEA,while 44.7% in intrahepatic cholangiocarcinoma group,the positive of CEA is significantly higher in intrahepatic cholangiocarcinoma group (χ2-28.946, P=0.000),the CEA is respectively 7.83,100,41.62±35.99in HCC and intrahepatic cholangiocarcinoma group. The positive of CA199 is higher in intrahepatic cholangiocarcinoma group (30.8% vs 67.5%,χ2=3.677, P=0.000). the CA199 is respectively 200.39±268.85. 3953.51±12151.27 in HCC and intrahepatic cholangiocarcinoma group,no Statistical differences among groups showed on the increase level of CA199 (t=-1.604, P=0.121)(3) Other clinical data4.3.1 Gender91 cases of hepatocellular carcinoma patients and 45 cases of intrahepatic cholangiocarcinoma were retrospectively investigated, by the HCC group of 83 males and 8 females, M/F=10/1;By the intrahepatic cholangiocarcinoma group of 27 males and 18 females, M/F=1.5/1. Statistical differences among groups showed on the gender (χ2=18.966, P=0.000)4.3.2 AgeIn HCC group,the patient aged 30-84, mean 52;In intrahepatic cholangiocarcinoma group,the patient aged 23-76, mean 55, no statistical differences among groups showed on the age (χ2=4.888, P=0.180). The prevalence increased with age, and it reached the peak at the age of 50-59 years in HCC group and 60 in intrahepatic cholangiocarcinoma group.4.3.3 Incidence of hepatitisThe incidence of hepatitis is 90.1 vs 37.8% in HCC and intrahepatic cholangiocarcinoma group, Statistical differences among groups (χ2=41.638, P=0.000)4.3.4 Incidence of liver cirrhosisStatistical differences among groups showed on the incidence of liver cirrhosis (x2=23.627, P=0.000),the incidence of liver cirrhosis is respectively 56.0% vs 13.3% in HCC and intrahepatic cholangiocarcinoma group.[Conclusions]1.18F-FDG PET/CT imaging is sensitve to the differentiation of tumor cell,well-differentiated hepatocellular carcinoma would be ignored in PET/CT scans because of low 18F-FDG uptake, so it is key to analyze the synthetic examinations for diagnosing.2.18F-FDG PET/CT imaging is is sensitive in detecting intrahepatic cholangiocarcinoma, the lesion showed high 18F-FDG uptake,which can be used for the diagnosis of intrahepatic cholangiocarcinoma.3. There is 1/3 HCC patients showed negative in 18F-FDG PET/CT imaging,the intrahepatic cholangiocarcinoma almost showed positive,if 18F-FDG PET/CT imaging is negative,the diagnosis of intrahepatic cholangiocarcinoma is excluded. 4. Intrahepatic cholangiocarcinoma always followed by intrahepatic bile ducts dilation.5. The positive of PET/CT was lower than contrast enhancement CT in HCC,by contrast,in intrahepatic cholangiocarcinoma.6. The incidence of lymph node and distant metastasis is higher in intrahepatic cholangiocarcinoma than in HCC,the lesion is more and wide distribution.7. The difference was not statistically significant between the two for incidence of vena cava and portal vein tumor thrombus.8. Hepatocellular carcinoma is associated with increasing of tumor markers AFP, intrahepatic cholangiocarcinoma is associated with increasing of tumor markers CEA and CA199. The incidence of male is higher in HCC,and always associated with hepatitis and liver cirrhosis9. It is very important to analyze the synthetic examinations for differential diagnosis of HCC and intrahepatic cholangiocarcinoma. |
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