The Role Of ¹⁸F-FDG PET/CT In Diagnosing Peritoneal Carcinomatosis In Patients With Undetermined Origin Of Ascites

[Objective]1. To assess the value of PET/CT for diagnosing peritoneal carcinomatosis in patients with undetermined origin of ascites.2. To evaluate the role of PET/CT in detection the primary tumor of peritoneal carcinomatosis.[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 November,2009. The clinical examination, X-Rays, B-ultrasound and serum tumor markers of all of 30 healthy subjects were normal1.2 patient groups70 patients with undetermined origin of ascites were enrolled in this study including 40 men and 30 women, aged from 23 to 79 years old, with a mean age of 57.3 years old. All of patients underwent whole body 18F-FDG PET/CT scan, serum tumor markers examination and cytological examination of ascites. The diagnosis of peritoneal carcinomatosis was established based on the histopathology examination with the sample obtained by the operation, abdominoscope, puncture biopsy and ascitic cytological examination. The primary cancer was diagnosed by the histopathology examination with the sample obtained by operation, abdominoscope, puncture biopsy, gastroscope and enteroscope. The diagnosis of benign ascites was established according to multiple negative findings of ascitic cytological examination, multi-modalities of imaging and clinical follow-up 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/CT images and CT images were interpreted independently by two experienced senior physicians of nuclear medicine and two experienced senior physicians of CT diagnosis. The diagnosis of PET/CT and CT were written independently by analyzing the imaging changes of PET/CT and CT. The information including disease history and the results of other examinations was analyzed when the physicians made the decision. The diagnosis of peritoneal carcinomatosis by PET/CT based on the following criteria:①Intense 18F-FDG uptake on the peritoneum was accompanied by obviously morphological abnormality in same region showed on the syn-modality CT.②When abnormal F-FDG uptake in the peritoneum was not accompanied by obviously morphological abnormality in the same region showed on syn-CT, the diagnosis of peritoneal carcinomatosis must be cautiously made by simultaneously analyzing the clinical data carefully.③If the obviously morphological abnormality in peritoneum on CT met the criteria of CT for diagnosing peritoneal carcinomatosis, the diagnosis of peritoneal carcinomatosis was established by CT even when no increased 18F-FDG uptake was seen in the same region on PET. The diagnosis of peritoneal carcinomatosis by CT based on the following criteria:①ascites,②obviously morphological abnormality in peritoneum including smudge, nodular and pastry thickening,③a stellate pattern in the mesentery,④peritoneum thickening including thickening of the perihepatic, subdiaphragmatic, anterior or lateral margins of the peritoneal cavity,⑤cystic lesion in the abdominal cavity,⑥thickening of small intestine wall and shifting location of intestine.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 peritoneum lesions with the most intense 18F-FDG uptake.②if the obviously morphological abnormality in peritoneum on CT was not 18F-FDG avid, ROIs were drawn on the areas with visible morphological abnormality and then copied to the same region on PET.③if no morphological abnormality and no abnormal 18F-FDG was seen, ROIs were drawn on the areas of mesentery or greater omentum guided by CT and then copied to the same region on PET. For the semiquantitative analysis, the size of ROIs was set at 4x4 pixels.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 independent-sample t-test was performed for statistical comparison of two independent samples of SUVmax. The different diagnostic efficacy of PET/CT, CT and cytological examination were compared and tested by McNemar's test. The agreement between different diagnostic methods was assessed with the weightedκstatistic for establishing their reliability in our study. The degrees of agreement were categorized as follows:κvalues between 0.00 to 0.40 was considered to be a poor agreement,κvalues between 0.41 to 0.70 to be a moderate agreement andκvalues between 0.71 to 1.00 to be a good agreement. 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. Findings of PET/CT in ascites group2.1 Diagnosis of peritoneal carcinomatosisIn the total of 70 patients enrolled,48 of them were proven to have malignant ascites caused by peritoneal cacinomatosis according to the histopathology examination.22 of them were proven to have benign ascites. SUVmax of peritoneal lesions in malignant ascites group and benign ascites group were 6.08±3.92 and 2.66±1.74 respectively(t=-5.063, P=0.000). In 70 patients enrolled, PET/CT diagnosed accurately in 43 patients with malignant ascites and in 20 patients with benign ascites. The false-negative and false-positive diagnosis occurred in 5 patients with malignant ascites and 2 patients with benign ascites. The sensitivity specificity and accuracy of PET/CT for diagnosing peritoneal cacinomatosis were 89.6%,90.9% and 90.0%, respectively. The syn-modality CT diagnosed accurately in 23 patients with malignant ascites and in patients with benign ascites. The false-negative and false-positive diagnosis occurred in 25 patients with malignant ascites and 4 patients with benign ascites. The sensitivity, specificity and accuracy of syn-modality CT for diagnosing peritoneal cacinomatosis were 47.9%,81.8% and 58.6%, respectively. The diagnostic efficacy of PET/CT is significantly higher than that of the syn-modality CT(χ2= 14.286, P=0.000).Among 70 patients, the cytological examination of ascites was positive in 21 patients with malignant ascites. The sensitivity, specificity and accuracy of the cytological examination for diagnosing peritoneal cacinomatosis were 43.8%,100% and 61.4%, respectively. The diagnostic efficacy of PET/CT is significantly higher than that of the cytological examination(χ2=13.885, P=0.000).The agreement between the diagnosis of PET/CT and final diagnosis was good (κ=0.776). However, the agreement between the diagnosis of CT and final diagnosis and that between cytological examination of ascites and final diagnosis were poor (κ=0.236 andκ=0.328). 2.2 Diagnosis of primary tumorsAmong 48 patients with peritoneal cacinomatosis, the primary tumor were found in 42 patients by analyzing the results obtained from operation, abdominoscope, puncture biopsy of liver, gastroscope and enteroscope. In the other 6 patients, the origin of the peritoneal carcinomatosis was failed to be found. The primary tumors were detected accurately by PET/CT in 38 patients. PET/CT showed false-negative in 4 patients with 2 of gastric signet-ring cell carcinoma,1 of cecal poorly differentiated adenocarcinoma combined with signet-ring cell carcinoma and 1 of malignant mixing germinoma. The primary tumors were detected by syn-modality CT in 23 patients. Detection rate of PET/CT for the primary tumors was 79.2%, which was similar to that obtained by combining the results of multiple examinations(79.2% vs.87.5%,χ2=2.250, P=0.125). Detection rate of syn-modality of CT was 54.8% which was much lower than that of PET/CT (x2=9.389, P=0.000).2.3 Distribution of peritoneal cacinomatosis2.3.1 The peritoneal cacinomatosis displayed as nodule, mass or diffuse infiltration with 18F-FDG avid in the most of lesions on PET/CT images and some only showed increased uptake of 18F-FDG. The peritoneal cacinomatosis mostly located in the greater omentum (81.3%), followed by in the mesentery (66.7%), the pouch of Douglas(50.0%), other peritoneum in the pelvis(33.3%) and right subphrenic space(20.8%). A few lesions can be found in left lateral margins (8.3%), anterior aspect of the peritoneal cavity (8.3%), left paracolic gutters(6.3%), and the ileo-cecal junction(4.2%).2.3.2 Distribution of peritoneal cacinomatosis in special tumorsGreater omentum was mostly involved by the gastric cancer, followed by the mesentery. In ovarian cancer, the lesions of peritoneal cacinomatosis often located in greater omentum and the pouch of Douglas. However, the mostly involved regions were greater omentum, mesentery and the pouch of Douglas in the patients with colon carcinoma and hepatocarcinoma.[Conclusions]1. In the present study,18F-FDG PET/CT plays an important role in diagnosing peritoneal carcinomatosis in patients with undetermined origin of ascites, and it can be used to differentiate the ascites.2. The metabolism of carcinoma is similar to its metastasis, so the whole-body PET/CT scans is superior to detecting primary tumor of peritoneal cacinomatosis. 3. Mucinous adenocarcinoma and signet-ring cell carcinoma would be ignored in PET/CT scans because of low F-FDG uptake, and the tuberculous peritonitis is usually be misdiagnosed, so it is key to analyze the synthetic examinations for diagnosing.