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Unlabelled: Although researched for many years, the prognostic value of tumor angiogenesis reflected by microvessel density (MVD) is still controversial, and there have been no previous reports regarding the correlation with 18F-FDG uptake in lung adenocarcinomas. Therefore, in the present study, we investigated the correlation between MVD determined with different endothelial cell antibodies and 18F-FDG uptake and compared the prognostic impact of those factors in lung adenocarcinomas., Methods: Forty-four patients with 45 lung adenocarcinomas underwent 18F-FDG PET before surgery. Consecutive paraffin-embedded sections obtained from each resected tumor were immunostained for CD31 (a panendothelial cell marker), CD105 (a proliferation-related endothelial cell marker), and CD34/alpha-SMA (for double labeling of endothelial cells and mural cells). Four high-power fields in the area with the highest MVD were selected for analysis. Computer-assisted image analysis was used to assess MVD., Results: MVD staining results for panendothelial cell markers can be classified into 3 microvessel patterns: diffuse, alveolar, and mixed. The highly ordered alveolar pattern is believed to represent preexisting alveolar vessels trapped in lung adenocarcinomas and may have no significant meaning for the aggressiveness of tumors. Preexisting alveolar cells also do not contribute to 18F-FDG uptake. CD105 staining of MVD (CD105-MVD) showed a significantly positive correlation with 18F-FDG uptake (P < 0.0001), whereas CD31 staining of MVD (CD31-MVD) showed a marginally negative correlation with it (P = 0.057). Although CD105-MVD correlated negatively with prognosis, patients with low CD105-MVD, compared with those with high or moderate CD105-MVD, had a much better prognosis in both disease-free and overall survival analyses (P = 0.017 and P = 0.013, respectively). Patients with low CD31-MVD had the worst prognosis (P = 0.032 for disease-free survival analysis and P = 0.179 for overall survival analysis)., Conclusion: There is no positive correlation between 18F-FDG uptake and MVD determined with panendothelial cell markers (CD31 and CD34); in contrast, there is a marginally negative correlation between them. MVD determined with CD105, which is a proliferation-related endothelial cell marker, reflects active angiogenesis, correlates positively with 18F-FDG uptake, and is a better indicator of prognosis in lung adenocarcinomas.

Unlabelled: Intratumoral lymphatic vessel invasion and lymph node involvement are important factors in the planning of therapeutic strategies, particularly limited surgical resection in patients with non-small cell lung cancer. (18)F-FDG uptake within the primary lesion correlates with aggressiveness on PET studies. The more metabolically active the tumor, the more aggressive are the findings. The aim of this multicenter study was to determine whether (18)F-FDG uptake of the primary tumor is a predictor of intratumoral lymphatic vessel invasion and lymph node metastasis in patients with non-small cell lung cancer., Methods: One hundred thirty-two patients with lung cancer were studied. All patients underwent a thoracotomy within 4 wk of the (18)F-FDG PET study. A 3-point visual scoring system (low, moderate, or high grade in comparison with mediastinal activity) was used to interpret (18)F-FDG uptake within the primary lesions. The degree of (18)F-FDG uptake in the primary tumor was correlated with the incidence of intratumoral lymphatic vessel invasion and lymph node involvement. Multivariate analysis was performed with logistic multivariate analysis to assess the joint effects and interactions of the variables (age, sex, tumor size, histology, and (18)F-FDG uptake) on intratumoral lymphatic vessel invasion and lymph node involvement., Results: Intratumoral lymphatic vessel invasion and lymph node involvement were found in 7.1% and 5.9%, respectively, of the patients classified in the low-grade group, and in 14.3% and 10.0%, respectively, of the patients classified in the moderate-grade group. In contrast, of the patients classified in the group with high (18)F-FDG uptake, intratumoral lymphatic vessel invasion and lymph node involvement were found in 39.7% and 38.9%, respectively. Multivariate analysis showed that only (18)F-FDG uptake was a significant factor for intratumoral lymphatic vessel invasion and that tumor size and (18)F-FDG uptake were significant factors for lymph node involvement. Of the patients in the high-grade group whose tumors were classified as > or =3 cm in size, lymph node involvement was found in 51.5%. In contrast, of the patients in the low- to moderate-grade group whose tumors were classified as <3 cm in size, lymph node involvement was found in only 9.1% (P < 0.0001)., Conclusion: Patients with a low to moderate (18)F-FDG uptake in the primary lesion had a significantly lower risk of concurrent intratumoral lymphatic vessel invasion and nodal involvement than did patients with a high (18)F-FDG uptake. In patients with non-small cell lung cancer, (18)F-FDG uptake by the primary tumor is a strong predictor of intratumoral lymphatic vessel invasion and lymph node metastasis.

Unlabelled: It has been reported that (18)F-FDG uptake, lactate concentration, and choline concentration are good indicators of malignant grade in several different kinds of tumors. In this study, we investigated the correlation between (18)F-FDG uptake in (18)F-FDG PET imaging, lactate concentration and choline concentration measured by in vitro (1)H magnetic resonance spectroscopy (MRS), and survival probabilities in human lung adenocarcinoma., Methods: Nineteen patients with lung adenocarcinoma underwent (18)F-FDG PET before surgery. The (1)H MRS spectra were obtained in vitro from methanol-chloroform-water extracts of lung adenocarcinomas and normal lungs. The ratios of the lactate (R(lac)) or choline (R(cho)) concentration of lung adenocarcinoma to normal lung from the same patient were correlated with the mean standardized uptake value (SUV). The Kaplan-Meier life table method was used to analyze the relationship between (18)F-FDG uptake, R(lac), R(cho), and patient survival probabilities., Results: There was no significant correlation between mean SUV and R(lac) or R(cho) in patients with lung adenocarcinoma. An SUV > 5 means poorer survival probabilities in patients with lung adenocarcinoma (P = 0.004). A higher R(lac) probably indicates a trend for patients with lung adenocarcinoma to have poorer survival probabilities; however, R(cho) is not an indicator of survival probability. (18)F-FDG uptake significantly correlated with cell differentiation (P = 0.007), whereas R(lac) and R(cho) had no correlation with it., Conclusion: No significant correlation was found between SUV and R(lac) or R(cho) in patients with lung adenocarcinoma. Compared with R(lac) and R(cho) measured by in vitro MRS, (18)F-FDG uptake is a better indicator of prognosis in patients with lung adenocarcinoma.

Unlabelled: Among patients with resected non-small cell lung cancer (NSCLC), approximately 50% present with a recurrent tumor. The clinical or pathologic TNM staging does not always provide a satisfactory explanation for differences in relapse and survival. Thus, it is of major importance to be able to predict these relapses and to prevent them with an active chemotherapy or radiotherapy program (or both). 18F-FDG uptake on PET could be of prognostic significance in patients with resected NSCLC. The goal of this study was to determine whether the level of metabolic activity observed with 18F-FDG uptake correlates with the probability of postoperative recurrence in patients with NSCLC., Methods: Fifty-seven patients with NSCLC were examined with 18F-FDG PET. For semiquantitative analysis, standardized uptake values (SUVs) were calculated. Patients were classified into high-SUV (> 5.0) and low-SUV (< or = 5.0) groups. All patients underwent thoracotomy within 4 wk after the 18F-FDG PET study. Tumor 18F-FDG uptake (SUV), pathologic stage, and lesion size were analyzed for their possible association with disease-free survival., Results: Forty-six patients had pathologic stage I NSCLC and 11 had pathologic stage II or stage III NSCLC. In a univariate analysis, patients with an SUV of < or = 5 had a much better disease-free survival than did patients with an SUV of > 5 (P < 0.0001). In patients with pathologic stage I and stage IA NSCLC, the SUV was also correlated with disease-free survival (P < 0.0001 and P = 0.0012, respectively). Patients with pathologic stage I disease had an expected 5-y disease-free survival rate of 88% if the SUV was < or = 5 and a survival rate of < or = 17% if the SUV was > 5. A multivariate Cox analysis identified the SUV as the most significant independent factor for disease-free survival., Conclusion: We conclude that the 18F-FDG uptake in primary NSCLC determined by PET has a significant independent postoperative prognostic value for recurrence, especially in patients with pathologic stage I NSCLC. 18F-FDG uptake was superior to pathologic stage in predicting relapse of patients with NSCLC.

Unlabelled: Recent reports have indicated the value of [(18)F]FDG PET and (201)Tl SPECT in diagnosing lung cancer. In this study, we compared the diagnostic value of FDG PET and (201)Tl SPECT in the evaluation of pulmonary nodules., Methods: Sixty-three patients with 66 pulmonary nodules suspected to be lung cancer on the basis of chest CT were examined by FDG PET and (201)Tl SPECT (early and delayed scans) within a week of each study. For semiquantitative analysis, the standardized uptake value (SUV) or the tumor-to-nontumor activity ratio (T/N) (or both) was calculated. All of these lesions were completely removed thoracoscopically or by thoracotomy and were examined histologically., Results: Fifty-four nodules were histologically confirmed to be malignant tumors, and 12 were benign. Both techniques delineated focal lesions with an increase in tracer accumulation in 41 of 54 lung cancers. (201)Tl SPECT on early or delayed scans (or both) identified 4 additional lung cancers that FDG PET images did not reveal: 3 bronchioloalveolar carcinomas and a well-differentiated adenocarcinoma. FDG PET identified 3 additional lung cancers that (201)Tl SPECT images did not reveal; 2 of these lung cancers were <2 cm in diameter. The mean FDG SUV and T/N of bronchioloalveolar carcinomas (2.06 +/- 0.76 and 3.49 +/- 1.03, respectively) were significantly lower than those of poorly differentiated adenocarcinomas (5.55 +/- 2.01 [P = 0.026] and 8.23 +/- 2.16 [P = 0.01], respectively). However, no significant difference was found in (201)Tl T/N on early and delayed scans between bronchioloalveolar carcinomas (1.64 +/- 0.29 and 1.87 +/- 0.42, respectively) and poorly differentiated adenocarcinomas (1.58 +/- 0.32 and 2.76 +/- 1.36, respectively). Of the 12 benign nodules, FDG PET and (201)Tl SPECT showed false-positive results for the same 7 benign nodules (58.3%) (4 granulomas, 1 sarcoidosis, 1 inflammatory pseudotumor, and 1 aspergilloma). Negative FDG PET findings and positive (201)Tl SPECT findings were obtained only for bronchioloalveolar carcinomas or a well-differentiated adenocarcinoma but not for other histologic types of lung cancers or benign pulmonary nodules., Conclusion: No significant difference was found between FDG PET and (201)Tl SPECT in specificity for the differentiation of malignant and benign pulmonary nodules. The degree of differentiation of lung adenocarcinoma correlated with FDG uptake but not with (201)Tl uptake. Bronchioloalveolar carcinoma (a well-differentiated, slow-growing tumor) findings typically were positive with (201)Tl but were negative with FDG. The combination of FDG PET and (201)Tl SPECT may provide additional information regarding the tissue characterization of pulmonary nodules.

Unlabelled: The goals of this study were to correlate FDG uptake with cell proliferation and cellular density in non-small cell lung cancer., Methods: Thirty-one patients with 32 non-small cell lung cancers were examined with FDG PET. For semiquantitative analysis, standardized uptake values (SUVs) were calculated. All patients underwent thoracotomy within 4 wk after the FDG PET study. Cell proliferation was immunohistochemically assessed as the relative number of cells expressing the proliferating cell nuclear antigen ([PCNA] labeling index). Cellular density was also evaluated using light microscopy., Results: SUVs correlated significantly with PCNA labeling index (r = 0.740; P < 0.0001) but only weakly with cellular density (r = 0.392; P = 0.0266). High FDG uptake correlated with high PCNA expression. The PCNA labeling index and SUVs were significantly lower in bronchioloalveolar carcinomas (n = 8) (12.3 +/- 9.45% and 1.45 +/- 0.76, respectively) than in nonbronchioloalveolar carcinomas (n = 19) (33.5 +/- 21.8%, P = 0.015, and 3.75 +/- 1.93, P = 0.003, respectively). However, no significant differences in cellular density were seen between bronchioloalveolar carcinomas and nonbronchioloalveolar carcinomas., Conclusion: FDG uptake is related to cell proliferation rather than to the cellular density of non-small cell lung cancer.

Unlabelled: The goals of our study were to establish PET accuracy with 18F-fluorodeoxyglucose (FDG) in finding localized formations of bronchioloalveolar lung carcinoma (BAC) and to investigate the correlation between FDG uptake and the degree of cell differentiation in adenocarcinoma of the lung., Materials: Twenty-nine patients with 30 adenocarcinomas of the lung (7 bronchioloalveolar lung carcinomas, 9 well differentiated, 2 well-moderately differentiated, 11 moderately differentiated and 1 poorly differentiated) were studied. All patients underwent thoracotomies within 4 wk after the FDG PET study. For qualitative analysis, the degree of FDG activity in the tumors was visually scored using a five-point grading system: 0 = same to background activity, 1 = less than mediastinal blood-pool activity, 2 = same to mediastinal blood-pool activity, 3 = slightly greater than mediastinal blood-pool activity and 4 = substantially greater than mediastinal blood-pool activity. Foci of activity with Grades 2-4 were considered tumors. For semiquantitative analysis, standardized uptake values (SUV) were calculated., Results: In 7 BACs, 4 lesions (57%) showed negative results on FDG PET, while in 23 non-BACs, only 1 lesion (4%), which was a well-differentiated adenocarcinoma showed a negative result. BACs' mean visual score (1.43 +/- 1.27) was significantly lower than that of non-BACs (3.17 +/- 1.03) (p = 0.001). The BACs' mean SUV (1.36 +/- 0.821) was significantly lower than that of well-differentiated adenocarcinomas (2.92 +/- 1.28) (p = 0.014); the mean SUV of well-differentiated adenocarcinomas was significantly lower than that of moderately differentiated adenocarcinomas (4.63 +/- 1.86) (p = 0.031). No significant differences were apparent in average size among these three histologic types., Conclusion: A correlation was observed between FDG uptake and the degree of cell differentiation in adenocarcinoma of the lung. FDG PET may show negative results for BAC.

Unlabelled: We compared the diagnostic value of [18F]2-fluoro-2-deoxy-D-glucose (FDG) PET imaging and 201Tl SPECT imaging in the detection of primary lung cancer and mediastinal lymph node metastases., Methods: Thirty-three patients with histologically-proven primary lung cancer were examined with both FDG PET and TI SPECT (early and delayed scans) within a week of each study. For semiquantitative analysis, the tumor-to-nontumor activity ratio (T-to-N ratio) was calculated., Results: Although both techniques delineated focal lesions with an increase in tracer accumulation in 28 patients, PET identified three additional patients in whom Tl SPECT images did not visualize any lesions on both early and delayed scans. In the detection of lung cancer of less than 2 cm in size, FDG PET provided higher sensitivity (six of seven, 85.7%) than did Tl SPECT early scan (one of seven, 14.3%) and delayed scan (four of seven, 57.1%). Neither technique visualized any lesions in two patients who had bronchioloalveolar carcinoma. The T-to-N ratio was significantly higher with FDG PET (10.39 +/- 6.63) than it was with Tl SPECT (early scan, 2.37 +/- 0.86; delayed scan, 3.01 +/- 1.01) (p < 0.0001), whereas there was significant positive correlation between the FDG T-to-N ratio and the thallium T-to-N ratio (p < 0.01). Twenty-two patients had thoracotomies. Regarding the staging of mediastinal nodes, FDG PET detected mediastinal lymph node metastasis that was negative on Tl SPECT, whereas both techniques excluded tumor involvement in enlarged node at CT., Conclusion: Both techniques have clinical value for the noninvasive detection of primary lung cancer that is 2 cm or greater in diameter. However, if a PET camera is available, FDG PET is considered the method of choice for the evaluation of patients with suspected primary lung cancer that is less than 2 cm in diameter.