| Objectives Part one:To assess the accuracy of gross target volume delineation comparing pathologic examination with FDG PET and anatomic imaging in patients with esophageal carcinoma.To determine the optimal method of FDG PET to estimate the gross tumor length in esophageal carcinoma.Part two:To examine the extent of subclinical microscopic spread in esophageal squamous cell carcinomas in order to clarify the CTV margin;To assess the correlation between FDG uptake and the extent of microscopic spread.Part three:To evaluate whether the uptake of FDG in esophageal carcinoma correlated with tumor biological positivity.Materials/Methods Part one:Thirty-six patients with esophageal squamous cell carcinoma underwent transthoracic esophagectomy were enrolled.All patients underwent esophagogram,esophagoscope and PET/CT before operations.The lengths of GTVs determined with the four modalities(PET,CT,esophagram and endoscopy)were compared quantitatively and validated with the pathologic specimen. The length of the tumor measured by pathologic examination was ecorded as Lgross. GTVs were also delineated with 3 different methods(visual interpretation,SUV 2.5, 40%SUVmax)on FDG PET imaging,and the length of tumors were recorded as Lvis, L2.5and L40,respectively,and compared with Lgross.All PET data were reviewed again postoperation,and the GTV was delineated using various percentages of SUVmax.The optimal threshold SUV was generated when the length of PET matched to the Lgross. Part two:Esophagectomy specimens were prospectively collected from 43 patients (including 36 patients underwent FDG PET/CT scan)with primary esophageal squamous cell carcinoma.The specimens were then serially sectioned for histological examination.The microscopic spread were observed on the pathological section.the contraction of the specimens were corrected.Part three:Immunohistochemistry for Ki-67 and Survivin were performed on thirty-six esophagectomy specimens.The SPF,DI and AI from flow cytometry were determined.SUVmaxwere compared with proliferation and apoptosis determined by immunohistochemistry and flow cytometry.Results Part one:The Lgrosswas 54.8mm±19.8mm.54.9mm±17.9mm as determined by PET,59.4mm±24.4mm by CT,52.6mm±28.1mm by endoscopy,and 59.7mm± 26.6mm by esophagram respectively.The Lvis,L2.5and L40were 51.8mm±19.3mm, 54.9mm±17.9mm and 43.4mm±15.4mm,respectively.The Lvis(P=0.123)and L2.5 (P=0.957)were not significantly different from Lgross,L2.5appears more approximate to Lgross.The mean L40was significantly shorter than Lgross(P＜0.001).The mean optimal threshold was 23.81%±11.29%for all tumors.The correlation coefficients of the optimal threshold were -0.802,-0.561 with SUVmaxand Lgross,respectively.Part two:The most distant extent of multicentric neoplastic lesion beyond the gross tumor was 8.2cm proximally,and 7.5cm distally;5.0cm proximally and 6.4cm distally in severe dysplasia;direct invasion(1.3cm proximally and 1.5cm distally);Intramural metastasis(5.2cm proximally and 6.0cm distally);vessel tumor embolus(4.3cm proximally and 5.1 cm distally).The SUVmaxhad negative correlation with the most microscopic spread extent,but correlated with the T stage and vessel tumor embolus. Part three:Excellent correlations were found between SUVmaxmeasures of FDG uptake and Ki-67 label index(percentage of positive cells;SUVmaxversus Ki-67:r =0.562,P=0.028).The correlation between the SPF and FDG uptake was weaker and also reached statistical significance(SUVmaxversus SPF:r=0.503,P=0.041).The aneuploid tumor had higher SUVmaxthan diploid tumor(P=0.012).Neither Survivin expression nor AI correlated with FDG SUVmax.Conclusions Part one:The recommended CTV margin were＜4.3cm proximally and＜5.0cm distally in about 93%of cases of esophageal carcinoma.FDG PET/CT did not improve the accuracy in determining CTV of esophageal carcinoma.Part two: PET was the most accurate modality in the GTV delineation of esophageal carcinoma. SUV cut-off of 2.5 provides the closest estimation in this study.Part three:FDG PET may be used to indirectly assess proliferation positivity of esophageal carcinoma in vivo.
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