Clinical Application Of ¹⁸F-FDG PET/CT In The Diagnosis And Staging Of Colorectal Cancer

[Objective]1. To assess the value of PET/CT in the diagnosis of colorectal cancer.2. To evaluate the value of PET/CT in the clinical staging of colorectal cancer.[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 Colorectal cancer patient groups82 patients with clinical suspicion of colorectal cancer were enrolled in this study including 49 men and 33 women, aged from 24 to 84 years old, with a mean age of 59.2 years old. All of patients underwent whole body 18F-FDG PET/CT scan before sugrury. Primary tumor in all patients were dignosed by surgical pathology. Lymph nodes in all patients were dignosed by lymph node dissection and pathological diagnosis.All patients with metastasis by B-ultrasound, CT, MRI the whole body bone SPECT and several PET/CT imaing, clinical follow-up for more than 6 months..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 PETtracer (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 conditionsAll 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 18F-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 colorectal cancer by PET based on the following criteriaPrimarily Tumor:exclude the physiological uptake,the wall of the intestine with the most intense 18F-FDG uptake was considerd colorectal cancer. The intense I8F-FDG uptake invades through muscularis propria into the subserosa was considered T3, the intense 18F-FDG uptake invades other organs or structures and/or perforates visceral peritoneum was considered T4, otherwise was considered T1 or T2 (in accordance with CT criteria).Region lymph nodes and metastasis:exclude the physiological uptake, the intense 18F-FDG nodosity or massive uptake was considered metastasis.The diagnosis of colorectal cancer by CT in accordance with international(AJCC) TNM staging criteria based on the following criteriaTO:No evidence of primary tumor, T1:Tumor invades submucosa, T2:Tumor invades muscularis propria,T3:Tumor invades through muscularis propria into the subserosa,or into nonperitonealized pericolic or perirectal tissues,T4:Tumor directly invades other organs or structures and/or perforates visceral peritoneum. N:when the CT detection of single lymph nodes>5mm,. NO:No regional lymph node metastasis, N1 Metastasis in 1 to 3 regional lymph nodes, N2:Metastasis in 4 or more regional lymph nodesM:When the group found that more than 12 lymph nodes, other organs metastasis, ascites and other signs,MO:No ditant metastasis, M1:Distant metastasis.6. PET/CT staging criteria of the PreoperativeIn accordance with international(AJCC) TNM staging criteria as mentioned above.Ⅰ(T1-2NOM0),Ⅱ(T3-4NOM0),Ⅲ(anyTNl-2M0),IV(anyTNMl).7. Statistical analysisStatistical 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 different diagnostic primarily tumor and stanging efficacy of PET/CT and operative pathology examination,PET/CT and enteroscope were compared and tested by McNemar's test. P<0.05 was considered statistically significant. The agreement between different diagnostic methods was assessed with the weightedкstatistic for establishing their reliability in our study. The degrees of agreement were categorized as follows:кvalues between 0.00 to 0.40 was considered to be a poor agreement,кvalues between 0.41 to 0.70 to be a moderate agreement andкvalues between 0.71 to 1.00 to be a good agreement.[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. colorectal cancer group2.1 18F-FDG PET/CT diagnostic efficiencyIn the total of 82 patients with clinical suspicion of colorectal cancer,80 patients of lesions were confirmed by surgery and pathological examination of malignant lesions,the other 2 of them F-FDG PET/CT scans show high 18F-FDG uptake of lesions were proven to sigmoid colon inflammatory pseudotumor and ileocecal appendix mucocele according to the surgical pathology examination. The other PET/CT detection of colorectal cancer was 97.6%.2.2 By operation confirmed for 80 cases of colorectal cancer patients pathological examination80 cases of colorectal cancer primary tumor site:25 cases of rectal cancer,21 cases of sigmoid colon,5 cases of carcinoma of the rectum and sigmoid colon,5 cases of descending colon, transverse colon in 11 cases (including one case of transverse colon had two lesions, one case of transverse colon had transverse colon 1 lesion, ascending colon 2 lesions and sigmoid colon 1 lesion),11 cases of one case of ascending colon, ileocecal carcinoma in 2 cases. Surgical pathology found.84 lesion.80 cases of colorectal cancer primary tumor pathology:33 cases with well-differentiated adenocarcinoma,4 cases with mucinous adenocarcinoma,1 case with neuroendocrine differentiation; moderately differentiated adenocarcinoma in 21 cases,2 cases with mucinous adenocarcinoma;well-moderately differentiated adenocarcinoma in 17 cases,4 cases with mucinous adenocarcinoma; 4 cases with moderately-poorly differentiated adenocarcinoma; poorly differentiated adenocarcinoma in 2 cases,1 case associated with signet ring cell carcinoma; mucinous adenocarcinoma in 1 cases; 1 cases with signet cell carcinoma with mucinous adenocarcinoma; carcinoid in 1 cases.2.3 By operation confirmed for 80 cases of colorectal cancer patients PET/CT compared with surgical pathology2.3.1 The primary tumorSurgical pathology examination revealed 80 cases of colorectal cancer in 18F-FDG PET imaging was positive in 79 cases, the sensitivity of PET was 98.8%; one case of mucinous adenocarcinoma no significant 18F-FDG PET uptake, CT shows bowel wall limitations thickening, The sensitivity of the colorectal cancer was 100% by PET/CT. Surgical pathology examination revealed 84 lesions, PET/CT detection of 18F-FDG uptake in 83 lesions (98.8%), except 1 case of mucinous adenocarcinoma, the levels were high uptake, SUVmax was 14.5±7.7 (3.7-47.6).Surgical pathology examination revealed 80 cases of primary colorectal cancer, including 65 patients invades serosal and 15 cases do not invades serosal. PET/CT diagnosis of serosal invasion were 66 cases, consistent with the pathological examination were 60 cases (T3+4), inconsistent with the pathology in 6 cases (T1+2); another 14 cases of PET/CT tumor do not invade serosal, consistent with the pathology in 9 patients (T1+2), and there were five cases of pathological inconsistent (T3+4). The sensitivity and consistency of PET/CT diagnosis of depth of tumor invasion were 92.3% and 86.3%, moderately consistency with pathology (P=0.000, Kappa=0.537)2.3.2 regional lymph node metastasisBase on the case study,80 patients with colorectal cancer, surgical pathology examination revealed regional lymph node metastasis in 32 patients (40%).18F-FDG PET/CT detection of lymph node metastasis in 21 cases,11 cases of surgical pathology examination showed lymph node metastasis in patients but PET/CT scans does not show; 3 cases of 18F-FDG PET/CT imaging showed high 18F-FDG uptake of by surgery pathological examination confirmed inflammatory lymph node hyperplasia. The sensitivity, specificity and accuracy of PET/CT in 80 patients with lymph node were 65.6%,93.8% and 82.5%.Base on the lesion study, in 832 excised lymph nodes of 80 patients with the operation,113 of 832 lymph nodes metastasis were proved by surgical pathology examination.18F-FDG PET/CT scans showed high 18F-FDG uptake in the lymph nodes was 91 (some small lymph node metastases and fusion), in which 88 surgical pathology confirmed metastatic lymph nodes, and the other 3 lesions were confirmed lymphadenitis hyperplasia; 25 lesions of surgical pathology examination showed lymph node metastasis in patients but PET/CT scans does not show. The sensitivity, specificity and accuracy of PET/CT in 80 patients with lymph node were 77.9%, 99.6% and 96.6%.2.3.3 distant metastasis80 cases of colorectal cancer patients found 13 cases of liver surgery, including one case of PET/CT imaging was low I8F-FDG uptake, one case associated with lung metastasis; two cases of pulmonary metastasis, one case associated with bone metastasis; one case of bone metastasis, PET/CT imaging were positive. The sensitivity was 100% by PET/CT.16 patients with distant metastasis were confirmed by surgical pathology, B-ultrasound, CT, MRI, SPECT, several PET/CT imaing and clinical follow-up.2.3.4 TNM staging of colorectal cancer80 cases of colorectal cancer in patients with pathological stage,12 cases in I, 32 cases inⅡ,21 cases inⅢ,15 cases inⅣ; PET/CT staging,11 cases in I,38 cases inⅡ,15 cases inⅢ,16 cases inⅣ. The accuracy for PET/CT staging was 77.5% (62/80), moderately consistency with surgical pathology (P=0.000,κ=0.680).2.4 PET/CT compared with colonoscopy82 patients were confirmed by colonoscopy, only 1 patient inconsistent with the pathological examination, the other consistent with the pathological examination The detection rate of Detection rate of PET/CT for colonoscopy on colorectal cancer was 98.8, which was similar to that obtained by colonoscopy examinations (97.6% vs. 98.8%, P=1.000).2.5 CEA,CA19-9 tumor maker82 patients which clinical suspicion of colorectal cancer,74 patients make the line of CEA, CA19-9 tumor marker examination before PET/CT imaging,34 patients with CEA increased, of which 33 cases of PET/CT imaging detected one or more of the malignant tumor lesions, one case of PET/CT imaging for the positive diagnosis was confirmed by surgical pathology mucoceles, PET/CT detection rate of 97.1%.33 patients increased CA19-9,33 patients with PET/CT imaging were detected in malignant lesions, PET/CT detection rate of 100%.15 patients, while CEA and CA19-9 increased in 15 cases PET/CT imaging were detected in malignant lesions, PET/CT detection rate of 100%.[Conclusions]1.18F-FDG PET/CT imaging is sensitive in detecting colorectal cancer. Most lesions of colorectal cancer are high uptake of FDG..2.18F-FDG PET/CT imaging has important clinical value in staging of colorectal cancer.T staging:18F-FDG PET/CT imaging for colorectal cancer detected primary tumor high sensitivity, high sensitivity to infiltrate degree, with surgical pathology is a moderate 86.3% accuracy, consistency, N staging:Base on the case or lesion study,18F-FDG PET/CT imaging to regional lymph node metastasis sensitivity is low,M staging:Liver metastasis in colorectal cancer is the most common blood lines parts,18F-FDG PET/CT imaging liver metastasis of colorectal cancer detection rate is high, better than common image means (ultrasound,CT,MRI).3. Mucinous adenocarcinoma and signet-ring cell carcinoma would be ignored in PET/CT scans because of low 18F-FDG uptake, and the inflammatory and proliferative are usually be misdiagnosed, so it is key to analyze the synthetic examinations for diagnosing.