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1.
OBJECTIVES: Given the importance of inflammation in atherosclerosis, we sought to determine if atherosclerotic plaque inflammation could be measured noninvasively in humans using positron emission tomography (PET). BACKGROUND: Earlier PET studies using fluorodeoxyglucose (FDG) demonstrated increased FDG uptake in atherosclerotic plaques. Here we tested the ability of FDG-PET to measure carotid plaque inflammation in patients who subsequently underwent carotid endarterectomy (CEA). METHODS: Seventeen patients with severe carotid stenoses underwent FDG-PET imaging 3 h after FDG administration (13 to 25 mCi), after which carotid plaque FDG uptake was determined as the ratio of plaque to blood activity (target to background ratio, TBR). Less than 1 month after imaging, subjects underwent CEA, after which carotid specimens were processed to identify macrophages (staining with anti-CD68 antibodies). RESULTS: There was a significant correlation between the PET signal from the carotid plaques and the macrophage staining from the corresponding histologic sections (r = 0.70; p < 0.0001). When mean FDG uptake (mean TBR) was compared with mean inflammation (mean percentage CD68 staining) for each of the 17 patients, the correlation was even stronger (r = 0.85; p < 0.0001). Fluorodeoxyglucose uptake did not correlate with plaque area, plaque thickness, or area of smooth muscle cell staining. CONCLUSIONS: We established that FDG-PET imaging can be used to assess the severity of inflammation in carotid plaques in patients. If subsequent natural history studies link increased FDG-PET activity in carotid arteries with clinical events, this noninvasive measure could be used to identify a subset of patients with carotid atherosclerosis in need of intensified medical therapy or carotid artery intervention to prevent stroke.  相似文献   

2.
OBJECTIVES: We investigated factors for carotid artery inflammation by [(18)F]-fluorodeoxyglucose (FDG) positron emission tomography (PET). BACKGROUND: Inflammation is present in some atherosclerotic plaques. The FDG-PET is capable of identifying and quantifying vascular inflammation within atherosclerotic plaques. METHODS: The FDG-PET imaging was performed in 216 consecutive patients (63 +/- 9 years, men:women 147:69) for cancer screening. Vascular inflammation in carotid atherosclerosis was quantified by measuring the standardized uptake value (SUV) of FDG into the artery. RESULTS: Multiple stepwise regression analysis revealed significant relationships between SUV and waist circumference (p < 0.001), hypertensive medication (p < 0.001), carotid intima-media thickness (p < 0.001), high-density lipoprotein cholesterol (p < 0.01, inversely), homeostasis model assessment of insulin resistance (p < 0.05), or high sensitivity C-reactive protein (p < 0.05). Age- and gender-adjusted SUV of FDG was significantly higher (p < 0.0001) in proportion to the accumulation of the number of the components of the metabolic syndrome. Thus, the metabolic syndrome was associated with increased FDG uptake in carotid atherosclerosis. CONCLUSIONS: Our present study may suggest that the metabolic syndrome is associated with inflammation in carotid atherosclerosis. (Detection of Plaque Inflammation by Positron Emission Tomography (PET); http://www.clinicaltrials.gov/ct/show/NCT00114504; NCT00114504).  相似文献   

3.
OBJECTIVES: We investigated whether simvastatin attenuates plaque inflammation by using 18F-fluorodeoxyglucose positron emission tomography (18FDG-PET) co-registered with computerized tomography. BACKGROUND: Inflammation plays a key role in progression and destabilization of atherosclerotic plaque. 18F-fluorodeoxyglucose PET is a promising tool for visualizing inflammation of atherosclerotic plaque. Antiinflammatory action is one of the pleiotropic effects of statins. METHODS: Forty-three consecutive subjects, who underwent 18FDG-PET for cancer screening and had 18FDG uptakes in the thoracic aorta and/or the carotid arteries, were randomized to either statin group receiving simvastatin (n = 21) or diet group receiving dietary management only (n = 22). The maximum standardized uptake values (SUVs) were measured in individual plaques, and were averaged for analysis of the subjectwise results. The responses were assessed after 3-month treatments. RESULTS: Positron emission tomography revealed 117 and 123 18FDG-positive plaques in the statin and diet groups, respectively. Simvastatin, but not diet alone, attenuated plaque (18)FDG uptakes and decreased the SUVs (p < 0.01). Simvastatin reduced low-density lipoprotein cholesterol (LDL-C) by 30% (p < 0.01) and increased high-density lipoprotein cholesterol (HDL-C) by 15% (p < 0.01), whereas LDL-C and HDL-C levels were not changed in the diet group. In the statin group, the decrease in the SUV was well correlated with the HDL-C elevation (p < 0.01) but not with the LDL-C reduction. CONCLUSIONS: 18F-fluorodeoxyglucose PET visualized plaque inflammation and simvastatin attenuated it. The LDL-C-independent effects of simvastatin may participate in the beneficial effect. 18F-fluorodeoxyglucose PET has a potential for visually monitoring plaque inflammation and the therapeutic effectiveness of statins.  相似文献   

4.
OBJECTIVES: This study tested the near-term reproducibility of (18)fluorodeoxyglucose positron emission tomography (FDG-PET) imaging of atherosclerosis. BACKGROUND: It is known that FDG-PET can measure inflammation within the aorta, carotid, and vertebral arteries with histologic validation in humans and animal models of disease. By tracking changes in inflammation over time, PET could be used as a surrogate marker of antiatheroma drug efficacy. However, the short-term variability and reproducibility of the technique are unknown. METHODS: We imaged the carotid arteries and aorta in 11 subjects with FDG-PET/computed tomography twice, 14 days apart. We assessed interobserver and intraobserver agreement and interscan variability. RESULTS: Interscan plaque FDG variability over 2 weeks was very low; intraclass correlation coefficients (ICC) ranged between 0.79 and 0.92. Interobserver agreement was high across all territories imaged except aortic arch (ICC values from 0.90 to 0.97, arch 0.71). Intraobserver agreement was high, with ICC values between 0.93 and 0.98. CONCLUSIONS: Spontaneous change in plaque FDG uptake is low over 2 weeks, with favorable inter- and intraobserver agreement. Power calculations suggest that drug studies using FDG-PET imaging would require few subjects compared with other imaging modalities. This study strengthens the case for FDG-PET as a noninvasive plaque imaging technique.  相似文献   

5.
BACKGROUND: Non-invasive methods of evaluating atherosclerosis in humans and experimental animals are needed. Studies indicate that FDG-PET has a potential to detect vulnerable, inflamed atherosclerotic lesions. METHODS: Nine atherosclerotic apoE-deficient mice were PET scanned. Four to determine optimal timing for imaging, and five post mortem after 1h redistribution of FDG and again after sequential removal of the interscapular brown fat and the atherosclerotic aortic arch. Uptake in various tissues in fasting (n=13) and non-fasting (n=7) apoE-deficient mice, including atherosclerotic and non-atherosclerotic aorta, was measured. Finally, accelerated atherosclerosis was induced by carotid ligation (n=12), and FDG-uptake was measured. RESULTS: FDG accumulation initially thought to correspond to the atherosclerotic aortic arch was recorded. Removal of interscapular brown fat, but not atherosclerotic aortic arch, removed the signal. The aortic arch accumulated less FDG than the non-atherosclerotic thoracic aorta both in fasting (ratio 0.5, p=0.008) and non-fasting (ratio 0.33, p=0.02) conditions. Carotid atherosclerosis likewise failed to increase FDG-uptake compared to the non-ligated artery (ratio 1.03). CONCLUSION: Spontaneously developed advanced atherosclerotic lesions in aorta were, paradoxically, associated with reduced FDG uptake, and accelerated carotid atherosclerosis also failed to increase FDG-uptake. The results seriously question the potential of FDG-PET for imagining of advanced, vulnerable atherosclerotic lesions.  相似文献   

6.
Inflammation of the arterial wall has been demonstrated by 18 Fluoro-Deoxyglucose PET imaging in patients with Takayasu's and temporal arteritis. We used ultrasonography and FDG-PET for structural and metabolic imaging of the carotid artery to diagnose giant cell arteritis without biopsy. In a 72 years old patient with isolated clinical and paraclinical signs of severe systemic inflammation ultrasonogaphy showed concentric hypoechogenic mural thickening of the carotidarteries and high FDG uptake in the left carotid, both axillary and subclavian arteries and the aorta. Clinical and paraclinical abnormalities showed a typical response to steroid treatment. In conclusion a combined approach using ultrasound and FDG-PET seems to be helpful in the diagnosis of GCA of large arteries particularly in patients with atypical manifestations of the disease and negative or unavailable biopsy of the temporal artery.  相似文献   

7.
PURPOSE: To study the potential of integrated positron emission tomography and computed tomography (PET/CT) to identify aneurysm wall inflammation. METHODS: The level of F18-fluorodeoxyglucose (FDG) uptake was studied in aneurysmal and normal-sized aortas of 34 male patients [17 with abdominal aortic aneurysm (AAA) and 17 age-matched controls] identified in a database of 278 consecutive patients evaluated for staging of primary lung cancer. The maximal standardized uptake value (SUV) was calculated to quantify FDG uptake in the AAA wall. RESULTS: AAAs showed significantly higher FDG uptake than the normal-sized aorta in age-matched controls (SUV 2.52+/-0.52 versus 1.78+/-0.45, respectively; p<0.001). The level of FDG uptake did not correlate with maximal aneurysm diameter (r=0.09; 95% CI -0.42 to 0.56; p=0.7). CONCLUSION: FDG-PET/CT is a promising technique to identify inflammation of the aneurysm wall. Irrespective of aneurysm diameter, asymptomatic AAAs show more FDG uptake and more inflammatory activity in the wall than the non-dilated abdominal aorta of sex/age-matched controls. Future studies will be directed at the predictive value of increased FDG uptake for aneurysm wall strength, rupture risk, and the utility of FDG-PET/CT in assessing the effect of medical interventions.  相似文献   

8.
There is an increasing body of evidence that a dynamic inflammatory process plays a role in the initiation, progression and destabilization of atherosclerotic plaques. The biological composition and inflammatory state of an atherosclerotic plaque, rather than the degree of stenosis or its size, are the major determinants of life-threatening events, such as ischemic cerebrovascular accident and acute coronary syndrome. To date, there is no non-invasive method clinically available for visualizing inflammation of individual plaques. Recently, we and others have shown that 18(F)-fluorodeoxyglucose (FDG) uptake, namely inflammation, can be evaluated quantitatively in the aortic, carotid, iliac and femoral plaques by using FDG positron emission tomography (PET) co-registered with computed tomography (FDG-PET/CT). Therefore, FDG-PET/CT, a combined functional and structural wholebody imaging modalities, holds great promise for non-invasive evaluation of inflammation – namely, activity – of atherosclerotic plaques of large arteries.  相似文献   

9.
OBJECTIVE: The usefulness of 18F-fluoro-2-deoxyglucose positron emission tomography (18FDG-PET), whose high rate of FDG accumulation indicates high metabolism and malignant potential, has already been reported. The aims of this study were to evaluate the malignancy of primary gastrointestinal stromal tumour (GIST) in the stomach by 18FDG-PET and to correlate the FDG uptake values with known risk factors as determined by histology after EUS-guided fine needle aspiration (EUS-FNA) or endoscopic biopsy. MATERIAL AND METHODS: Of 29 patients with histologically proven GI-mesenchymal tumours, 21 with gastric GISTs underwent 18FDG-PET. Tumour size, mitotic index, Ki-67 labelling index (LI) and cellularity of the tumour tissue were compared with the standardized uptake value (SUV) of FDG. RESULTS: Strong correlations were found between the SUV of FDG and EUS size, and mitotic index of EUS-FNA specimens (tumour size versus SUV, p=0.004, r=0.542; number of mitotic cells versus SUV, p=0.0078; n=21). Moreover, we examined the association between SUV and risk categories based on EUS-FNA findings using ROC curves. The cut-off values of FDG SUV were 2.2, 4.2 and 6.5 for the very low-, low-, intermediate- and high-risk groups, respectively. CONCLUSIONS: 18FDG-PET may be used to assess malignancy of GISTs. This image modality helps us determine the management strategy for these patients and complements the information on the biological behaviour and cellular proliferation of the tumours.  相似文献   

10.
Use of 18FDG-PET for malignant tumors of the pleura raises certain technical difficulties because of the small size of the tumors and their diffuse distribution, but hybrid PET/CT machines offer a better localization of FDG uptake. FDG-PET can discriminate between malignant and benign pleural tumors FDG uptake in the pleura is the best diagnostic criteria of malignancy. The presence of FDG uptake in pleural effusion is less discriminate between benign and malignant disease. For mesotheliomas, FDG-PET can difference malignant tumors from benign tumors of the pleura on the basis of the SUV value ( 2). It does not enable detection of mediastinal node involvement and regional extension but is effective in detecting extra-thoracic regional spread not identified with other imaging methods. FDG-PET can thus affect the therapeutic strategy. The intensity of uptake has prognostic value. SUV<4 associated with an epithelial tumor is a sign of good prognosis at three years. SUV > 4 associated with a non-epithelial tumor is a sign of poor prognosis. For mesotheliomas, FDG uptake can be used to assess the effect of chemotherapy and determine whether patients are good responders or not.  相似文献   

11.

Background/Purpose

Pancreatic carcinoma has a poor prognosis, and early detection is essential to allow potentially curative resection. Despite the wide array of diagnostic tools available, the detection of small pancreatic tumors remains difficult. The aim of this study was to investigate the contribution of 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) to the diagnosis of early pancreatic cancer.

Methods

FDG-PET was performed in 56 patients with pancreatic cancer who underwent curative surgery. The standardized uptake value (SUV) for FDG was calculated in each patient and the relationships between the SUV and various clinicopathological factors were analyzed.

Results

The tumors ranged from 0.8 to 6.5 cm in diameter. When the cutoff value for the SUV was set at 2.5, 51 of the 56 patients (91%) had a positive FDG-PET study. The SUV did not show a significant difference in relation to tumor differentiation or pTS and pT factors. There was also no correlation between the SUV and the maximum tumor diameter (r = 0.22; P = 0.1). Five tumors had an SUV below the cutoff value, and all of these lesions had intermediate or scirrhous stroma rather than medullary stroma.

Conclusions

These results indicate that FDG-PET is useful for the detection of small early pancreatic cancers.  相似文献   

12.
OBJECTIVES: We examined whether right ventricular (RV) [(18)F]fluorodeoxyglucose (FDG) accumulation is increased in patients with pulmonary hypertension using gated positron emission tomography (PET) and whether RV FDG accumulation changes after therapy with epoprostenol. BACKGROUND: Myocardial glucose utilization is increased in animal models with ventricular pressure overload. METHODS: We performed gated FDG-PET in 24 patients with pulmonary hypertension. The RV standardized uptake value (SUV) of FDG was corrected for the partial volume effect based on the wall thickness measured by electron-beam computed tomography or magnetic resonance imaging. RESULTS: The corrected RV SUV of FDG was significantly correlated with the pulmonary vascular resistance, mean pulmonary artery pressure, right atrial pressure, RV wall stress, and plasma brain natriuretic peptide levels, but not with the RV wall thickness and mass. After pulmonary vasodilator therapy with epoprostenol for three months, the corrected RV SUV of FDG significantly decreased in the responders, but not in the non-responders, and the percentage change of the corrected RV SUV of FDG was significantly correlated with the percentage change of the pulmonary vascular resistance (r = 0.78; p < 0.01) and RV systolic wall stress (r = 0.76; p < 0.05). CONCLUSIONS: The RV FDG accumulation corrected for the partial volume effect was significantly increased in accordance with the severity of the RV pressure overload (i.e., the RV peak-systolic wall stress) in patients with pulmonary hypertension. Furthermore, the corrected RV FDG accumulation was decreased after the treatment with epoprostenol in accordance with the degree of reduction in the pulmonary vascular resistance and RV peak-systolic wall stress.  相似文献   

13.
Atherosclerosis is an inflammatory disease that causes most myocardial infarctions, strokes and acute coronary syndromes. Despite the identification of multiple risk factors and widespread use of drug therapies, it still remains a global health concern with associated costs. Although angiography is established as the gold standard means of detecting coronary artery stenosis, it does not image the vessel wall itself, reporting only on its consequences such as luminal narrowing and obstruction. MRI and computed tomography provide more information about the plaque structure, but recently positron emission tomography (PET) imaging using [(18) F]-fluorodeoxyglucose (FDG) has been advocated as a means of measuring arterial inflammation. This results from the ability of FDG-PET to highlight areas of high glucose metabolism, a feature of macrophages within atherosclerosis, particularly in high-risk plaques. It is suggested that the degree of FDG accumulation in the vessel wall reflects underlying inflammation levels and that tracking any changes in FDG uptake over time or with drug therapy might be a way of getting an early efficacy readout for novel anti-atherosclerotic drugs. Early reports also demonstrate that FDG uptake is correlated with the number of cardiovascular risk factors and possibly even the risk of future cardiovascular events. This review will outline the evidence base, shortcomings and emerging applications for FDG-PET in vascular imaging. Alternative PET tracers and other candidate imaging modalities for measuring vascular inflammation will also be discussed.  相似文献   

14.
Widespread plaque inflammation has been demonstrated in acute coronary syndromes (ACS). We evaluated signs of plaque inflammation in carotid arteries of patients with ACS by contrast-enhanced magnetic resonance imaging (MRI). Carotid MRI was performed in 13 patients with ACS and in 9 controls having at least 1 carotid plaque with a stenosis > or =40%. MRI criteria of plaque inflammation were: increased T2 signal >50% of the plaque areas (tissue oedema) and/or enhancement after gadolinium injection (neo-vascularization). MRI signs of inflammation were found in 95% and in 33% of patients with ACS and controls, respectively (p<0.001). Carotid artery MRI may serve as a window to the entire cardiovascular system, to identify "vulnerable" patients.  相似文献   

15.
The prognostic value of 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) in the assessment of post-treatment residual masses in patients with Hodgkin's disease (HD) or non-Hodgkin's lymphomas (NHL) was evaluated. We prospectively studied 58 patients with HD (n = 43) or NHL (n = 15) who had post-therapeutic complete remission with residual masses (CRu) indicated by computerized tomography. Analysis of 62 residual locations by FDG-PET was performed separately for HD and NHL. Patients with a PET-positive residual mass [standardized uptake value (SUV) > 3] had a recurrence rate of 62.5% (5/8 patients), whereas patients with PET-negative residual mass (SUV < or =3.0) showed a recurrence rate of 4% (2/50 patients, P = 0.004). A positive FDG-PET study correlated with a significantly poorer progression-free survival (P < 0.00001). No recurrence occurred in any of the 39 HD patients with a negative PET scan (negative predictive value, 100%). Four out of four NHL patients with a positive PET study relapsed (positive predictive value, 100%). In conclusion, FDG-PET is a suitable non-invasive method with a high degree of accuracy in the prediction of early recurrence in lymphoma patients with CRu.  相似文献   

16.
Conventional algorithms and noninvasive imaging tests for the identification of stable, hemodynamically significant coronary artery disease offer little insight into the detection of potentially vulnerable and inflamed coronary plaques, those most likely to rupture and cause acute coronary syndromes. Positron emission tomography (PET) with fluorodeoxyglucose (FDG) serves as a potential novel modality for the identification of plaque inflammation, as initial studies in animal and human studies have demonstrated that FDG uptake correlates with macrophage accumulation and inflammation. Therapy with anti-inflammatory agents has also been demonstrated in the arterial vasculature to reduce plaque FDG uptake. Although imaging of coronary inflammation with FDG-PET holds tremendous promise, several hurdles remain to be surmounted prior to widespread clinical application.  相似文献   

17.
Coronary inflammation is related to atherosclerotic disease and, less frequently, systemic vasculitis. Regardless of the etiology, coronary inflammation is associated with adverse cardiac events. Molecular imaging with 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET/CT) allows in vivo assessment of coronary inflammation and evaluation of response to therapy. The aim of this review is to give an update on the recent development of FDG-PET/CT, discuss the potential roles of coronary inflammation imaging, review the limitations of FDG-PET/CT imaging, and give an overview of the new tracers available for PET/CT plaque imaging.  相似文献   

18.
Purpose

Evidence suggests that the inflammatory state of an atherosclerotic plaque is important in predicting future risk of plaque rupture. This study aims to investigate the feasibility of measuring plaque inflammation in patients with obstructive sleep apnea (OSA) utilizing advanced vascular imaging — hybrid positron-emission tomography/magnetic resonance imaging (PET/MRI) with fluorodeoxyglucose (FDG) tracer—before and after continuous positive airway pressure (CPAP).

Methods

Patients with newly diagnosed moderate to severe OSA underwent baseline PET/MRI for assessment of vascular inflammation of the carotid arteries and thoracic aorta prior to initiation of CPAP. Those adherent to CPAP returned for repeat imaging after 3–6 months of CPAP use. Atherosclerotic plaque activity, as measured by arterial wall FDG uptake, was calculated using target-to-background ratios (TBR) before and after CPAP.

Results

Five patients were recruited as part of a focused project. Mean age was 52 years (80% male), and mean apnea-hypopnea index (AHI) was 33. Three patients were objectively adherent with CPAP. In the pre-CPAP phase, all patients had focal FDG uptake in the carotid arteries and aorta. After CPAP, there was an average reduction in TBR of 5.5% (TBRmean) and 6.2% (TBRmax) in carotid and aortic plaque inflammation, similar in magnitude to the reduction observed with statin therapy alone in non-OSA patients (previously reported by others).

Conclusions

We demonstrate the feasibility of using hybrid PET/MRI to assess atherosclerotic plaque inflammation in patients with OSA before and after CPAP. Use of the vascular PET/MRI platform in patients with OSA may provide better insight into the role of OSA and its treatment in reducing atherosclerotic inflammation.

  相似文献   

19.
Carotid ultrasound is a useful tool to detect plaque and measure carotid intimal-medial thickness (CIMT), which help identify asymptomatic patients at risk of cardiovascular events. However, the role of carotid ultrasound in stratifying risk in symptomatic patients has not been studied. We prospectively examined the hypothesis that in symptomatic patients undergoing exercise (or pharmacologic) stress testing (EST), CIMT and carotid plaque will improve the ability to identify patients with > or =50% coronary diameter stenosis. Mean and maximal CIMTs were measured in 50 symptomatic patients without known coronary artery disease (CAD) who were scheduled to undergo diagnostic angiography after EST with imaging. Pretest probability of CAD was calculated for each patient based on age, gender, and nature of symptoms. Fifty percent of patients were men, 32% were diabetic, 70% had hypertension, and 58% had dyslipidemia. CAD > or =50% was associated with CIMT in the >75th percentile (74% vs 44%, p = 0.047) and with presence of carotid plaque (96% vs 59%, p = 0.003). Of patients with an equivocal/negative EST result (n = 38), those with carotid plaque had a 46% (13 of 28) prevalence of significant CAD; in the smaller subset of patients without carotid plaque (n = 10), none had luminal stenosis > or =50% (p = 0.007). Pretest probability of CAD, presence of carotid plaque, moderately/severely abnormal EST result, and hypertension were independent predictors of significant CAD. In conclusion, carotid ultrasound appears to offer incremental value to EST in predicting presence or absence of > or =50% coronary diameter stenosis in symptomatic patients with equivocal/negative EST result.  相似文献   

20.
Objective. The usefulness of 18F-fluoro-2-deoxyglucose positron emission tomography (18FDG-PET), whose high rate of FDG accumulation indicates high metabolism and malignant potential, has already been reported. The aims of this study were to evaluate the malignancy of primary gastrointestinal stromal tumour (GIST) in the stomach by 18FDG-PET and to correlate the FDG uptake values with known risk factors as determined by histology after EUS-guided fine needle aspiration (EUS-FNA) or endoscopic biopsy. Material and Methods. Of 29 patients with histologically proven GI-mesenchymal tumours, 21 with gastric GISTs underwent 18FDG-PET. Tumour size, mitotic index, Ki-67 labelling index (LI) and cellularity of the tumour tissue were compared with the standardized uptake value (SUV) of FDG. Results. Strong correlations were found between the SUV of FDG and EUS size, and mitotic index of EUS-FNA specimens (tumour size versus SUV, p=0.004, r=0.542; number of mitotic cells versus SUV, p=0.0078; n=21). Moreover, we examined the association between SUV and risk categories based on EUS-FNA findings using ROC curves. The cut-off values of FDG SUV were 2.2, 4.2 and 6.5 for the very low-, low-, intermediate- and high-risk groups, respectively. Conclusions. 18FDG-PET may be used to assess malignancy of GISTs. This image modality helps us determine the management strategy for these patients and complements the information on the biological behaviour and cellular proliferation of the tumours.  相似文献   

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