Abstract
BackgroundSurgical resection remains the mainstay of curative treatment for intrahepatic cholangiocarcinoma (ICC). Prognosis after surgery is unsatisfactory despite improvements in treatment and post-operative clinical management. Despite developments in the molecular profiling of ICC, the preoperative prediction of prognosis remains a challenge. This study aimed to identify clinical prognostic indicators by investigating the molecular profiles of ICC and evaluating the preoperative imaging data of 18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET).MethodsA retrospective analysis was performed on 50 consecutive patients with ICC who underwent curative hepatectomy after 18F-FDG-PET examination. To evaluate the molecular profiles of ICC, KRAS mutation status was assessed in resected specimens. For the assessment of glucose uptake, we observed the expression of glucose transporter-1 (GLUT-1) by immunohistochemistry. The data of 18F-FDG-PET were re-evaluated as follows: maximum standardized uptake value, metabolic tumor volume (MTV), and total lesion glycolysis (TLG). Cut-off values were determined using receiver operating characteristic (ROC) curve analysis. Cumulative overall survival (OS) was analyzed using the Kaplan–Meier analysis.ResultsOverall, 16 (32.0%) patients had mutations in KRAS. Patients with mutated KRAS exhibited shorter OS than those with wild-type KRAS (5-year OS, 0% vs. 35.1%, P < 0.001). GLUT-1 expression was significantly higher in tumors with mutated KRAS than in tumors with wild-type KRAS (median, 4.0 vs. 1.0, P < 0.001). Survival was significantly different when stratified by expression of GLUT-1 (5-year OS, 0% vs. 46.5%, P <0.001). Among the 18F-FDG-PET parameters, the MTV and TLG were significantly higher in the mutated KRAS group than in the wild-type KRAS group (P = 0.013 and P = 0.026, respectively). ROC curve analysis revealed a cut-off value of 38 for the MTV, with the highest accuracy (area under the curve = 0.789; 95% confidence interval, 0.581–0.902) for predicting KRAS mutation. This cut-off value permitted stratification of OS (high vs. low: 5-year OS, 13.1% vs. 36.7%, P = 0.008).ConclusionsHigh MTV is associated with KRAS mutation and poor postoperative outcomes in patients with ICC, suggesting that the MTV of ICC measured by 18F-FDG-PET may provide useful information for tumor molecular profiles and prognosis.
Highlights
Surgical resection remains the mainstay of curative treatment for intrahepatic cholangiocarcinoma (ICC)
We investigated the presence of KRAS mutation, the expression of glucose transporter-1 (GLUT-1), and 18F-FDG-Positron emission tomography (PET) parameters in 50 ICC patients, and examined whether there was an association between ICC prognosis and these factors
No patients received any treatment before operation, and postoperative adjuvant chemotherapy was performed in 30 patients (60.0%)
Summary
Surgical resection remains the mainstay of curative treatment for intrahepatic cholangiocarcinoma (ICC). Prognosis after surgery is unsatisfactory despite improvements in treatment and post-operative clinical management. Despite developments in the molecular profiling of ICC, the preoperative prediction of prognosis remains a challenge. Surgical resection represents the curative treatment option, but surgery is only possible for selected patients. It is essential to develop a multidisciplinary strategy for ICC to improve prognosis [6,7,8,9]. New therapies based on the molecular or genetic characteristics of ICC have been developed. It should be possible to select the appropriate therapy for each patient depending on the molecular or genetic characteristics of their individual tumors. There is little biological information in ICC, so it is difficult to select treatment before surgery
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