肺動脈及肺部病灶之間的關係與肺動脈被包埋壓迫的程度可幫助鑑別
診斷良性或惡性病灶，但限於中央肺到離肋膜 2 cm 的病灶，可因此減少切
片取檢體的機會。除此之外，肺動脈與肺部病灶之間的關係也許可提供是 否有血管內侵犯的訊息，與不良預後有關係，但須進一步研究更多的樣本。
參考文獻
1. Laurent F, Montaudon M, Corneloup O. CT and MRI of lung cancer.
Respiration 2006;73:133-142.
2. Jeong YJ, Lee KS, Jeong SY, et al. Solitary pulmonary nodule:
characterization with combined wash-in and washout features at dynamic multi-detector row CT. Radiology 2005;237:675-683.
3. Carvalho P, Anderson DK, Charan NB. Bronchial arterial imaging using helical computed tomography. Pulm Pharmacol Ther. 2007;20:104-108.
4. Tan LL, Han MJ, Li YB, Jiang JD, Li SX, Zhou SP. Role of 16 slices spiral CT angiography with 3-dimensional CT and CT virtual endoscopy in
detecting blood supply of lung carcinoma. Ai Zheng 2007;26:73-77.
5. Chen H, Wang XH, Ma DQ, Ma BR. Neural network-based computer-aided diagnosis in distinguishing malignant from benign solitary pulmonary nodules by computed tomography. Chin Med J 2007;120:1211-1215.
6. Matsuki Y, Nakamura K, Watanabe H, et al. Usefulness of an artificial neural network for differentiating benign from malignant pulmonary nodules on
high-resolution CT: evaluation with receiver operating characteristic analysis.
AJR Am J Roentgenol 2002;178:657-663.
7. Zhang YK, Le HB, Chen ZH, Wang CY, Zhang BJ. Study on relationship between blood supply from pulmonary artery and pathological characteristics of patients with primary bronchogenic carcinoma. Chin J Lung Canc
29
8. Müller KM, Meyer-Schwickerath M. Bronchial arteries in various stages of bronchogenic carcinoma. Pathol Res Pract. 1978;163:34-46.
9. Schwartz AM, Henson DE, American College of Chest Physicians.
Diagnostic surgical pathology in lung cancer: ACCP evidence-based clinical practice guidelines (2nd edition). Chest 2007;132(3 Suppl): 78S-93S.
10. O’keefe ME Jr. Good CA, McDonald JR. Calcification in solitary nodules of the lungs. AJR Am J Roentgenol 1957;77:1023-1033.
11. Nathan MH, Collins VP, Adams RA. Differentiation of benign and
malignant pulmonary nodules by growth rate. Radiology 1962;79:221-231.
12. Hartman TE. Radiologic evaluation of the solitary pulmonary nodule.
Radiol Clin North Am. 2005;43:459-465, vii.
13. Wahidi MM, Govert JA, Goudar RK, Gould MK, McCrory DC. Evidence for the treatment of patients with pulmonary nodules: when is it lung
cancer? : ACCP evidence-based clinical practice guidelines (2nd edition).
Chest 2007;132:94S-107S.
14. Beigelman-Aubry C, Raffy P, Yang W, Castellino RA, Grenier PA.
Computer-aided detection of solid lung nodules on follow-up MDCT Screening: evaluation of detection, tracking, and reading Time. AJR Am J Roentgenol 2007;189:948-955.
15. Hsu WH, Yu YH, Tu CY, et al. Color Doppler US pulmonary artery vessel signal: a sign for predicting the benign lesions. Ultrasound in Med & Biol.
2007;33:379-388.
16. Shields TW. Prognostic significance of parenchymal lymphatic vessel and blood vessel invasion in carcinoma of the lung. Surg Gynecol Obstet 1983;157:185-190.
17. Ichinose Y, Yano T, Asoh H, Yokoyama H, Yoshino I, Katsuda Y.
Prognostic factors obtained by a pathologic examination in completely resected non-small-cell lung cancer. An analysis in each pathologic stage. J Thorac Cardiovasc Surg 1995;110:601-605.
18. Hansell DM, Wells AU. Towards complete and accurate reporting of studies of diagnostic accuracy: the STARD initiative. Clin Radiol 2003;58:573–574.
19. Landis JR, Koch GG. The measurement of observer agreement for categorical data. Biometrics 1977;33:159-174.
31
附錄 英文全文
Pulmonary artery related to lung lesion aids in differential diagnosis Abstract
Background and Purpose
Improvement of the resolution with rapid scanning in multidetector-row computed tomography (MDCT) increases accuracy to demonstrate the
relationship of pulmonary artery and lung lesion, even in the peripheral lung.
The aim of this study is to evaluate the ability of the relationship between pulmonary artery and lung lesion to distinguish benign lung lesion from malignancy and the degree of pulmonary arterial encasement in predicting malignancy is evaluated with receiver operating characteristic (ROC) curve.
Materials and Methods
A total of 100 lung nodules/masses of 16-slice MDCT data were included in this study. Dynamic CT images of 77 bronchogenic carcinomas and 23 benign lung lesions were independently assessed by 2 observers who were unaware of the final diagnosis of each lesion. They recorded the relationships of the lung lesion and adjacent pulmonary artery as encasement, displacement, penetration, in the margin and disconnection. Correlation of the relationships with the
pathologic findings was also performed. Fisher’s exact test and odds ratio (OR) with its 95% confidence interval (CI) were used to analyze the relationship of pulmonary artery to lesion with the possibility of malignancy. The degree of pulmonary arterial encasement in the benign lesion and malignancy was
evaluated by Wilcoxon rank sum test. The agreement between 2 observers was evaluated by kappa (κ) statistics. In addition, the sensitivity and specificity profiles of the degree of encasement in diagnosis of malignancy were determined by plotting an empirical ROC curve.
Results
The relationship between pulmonary arteries and lung lesions had a
statistically significant difference in benign from malignancy (p<0.001). [When using penetration as baseline; the OR for encasement was 18.1, (95% CI:
4.6-71.7, p< 0.001); the OR for displacement was 33.7, (95% CI: 5.3-213.7, p = 0.0002)]. Inter-observers’ agreement was very good (κ = 0.819; 95% CI:
0.718-0.919). The average degree of pulmonary arterial encasement in benign lesion and malignancy were 52.1 % ± 27.3 % and 71.8% ± 18.8%, respectively (p = 0.011). The ROC curve showed that the degree of pulmonary arterial
encasement has a moderate discriminating ability in diagnosing lung carcinoma, and the area under the curve was 0.738. The best cut-off value was 44.4%. All lesions with pulmonary arterial encasement had microscopic vascular invasion while lesions with pulmonary arterial penetration did not have vascular invasion.
Conclusions
The relationship of pulmonary artery to the lung lesion and degree of
pulmonary arterial encasement could be used in differentiating benignancy from malignancy not only for central lung lesions but also peripheral lung lesions and this would decrease biopsy rate. Furthermore, pulmonary arterial encasement
33
implies microscopic vascular invasion which is related to a poor prognosis.
Key words: Lung lesion; Pulmonary artery; Multidetector-row computed tomography (MDCT); Encasement; Displacement; Penetration
Introduction
Solitary pulmonary nodule/mass is a common radiological finding. The treatment plan differs according to the possibility of malignancy based on the radiological findings. Computed tomography (CT) is considered to be one of the most important non-invasive diagnostic tools in clinical practice. Several
morphologic features in CT, including spiculated borders, ill-defined contours, presence of air bubbles, eccentric calcifications, mixed solid and ground–glass, lesions > 7 mm in diameter(1), ≥ 25 Hounsfield units (HU) wash in and 5-31 HU washout of contrast medium in dynamic study (2) are suggestive of a malignancy. However, the parameters of benign lesions and malignancy have some areas of overlap.
The lung, like the liver has dual blood supply from bronchial artery and pulmonary artery. Generally, the bronchial artery provides the blood supply to the bronchogenic carcinoma and the pulmonary artery, like the portal vein, is easy to be involved by the parenchymal lesion. It is already established that vascular encasement by tumor is more likely a malignancy and penetration is more likely a benign lesion. Using the relationship of the bronchial artery to lung lesions in distinguishing benignancy from malignancy in 16-slice
multidetector CT (MDCT) usually has limitations. This is because tracing the whole course of the bronchial artery to the lung carcinoma still a challenge in 16-slice MDCT as our preliminary study, even though a high detection rate was
35
benign lesions (3) and the morphology of these benign lesions may mimic malignancy.
When a lung cancer invasion the large blood vessels of the mediastinum, it is staged as T4 according to TNM malignant cancer staging system. Chen et al (5) and Matsuki et al (6) included the relationship of nodule to both pulmonary artery and vein to distinguish benign from malignancy. However, the pulmonary vein is easy to be encased or compressed or invaded by tumor and non-tumor lesions due to low blood pressure that we couldn’t use a collapsed pulmonary vein to differential benign from malignant lesions in our preliminary study.
Pathologic studies reported that the pulmonary artery also supplies the bronchogenic carcinoma (7) and there are anastomoses between the pulmonary artery and the bronchial artery in bronchogenic carcinoma in the growth zone as tumor growth (8). However, this is rarely demonstrated with radiological images possibly due to poor tissue contrast between carcinoma and parenchyma during pulmonary artery angiography. Pulmonary artery like portal vein can be encased by the cholangiocarcinoma or pancreatic carcinoma and can even be invaded by hepatocellular carcinoma that is usually encased or invaded by lung carcinoma.
Pulmonary artery has a relative high blood pressure than pulmonary vein that may not too easily to be compressed and may be used to differential benign from malignancy.
Improvement of the temporal and spatial resolution in MDCT with rapid cover of the whole thorax combined with power auto-injector and CT software
technique (Smart Prep; GE Medical Systems) to time the initiation of scanning in consideration of peak enhancement that the pulmonary artery could be
demonstrated clearly, even in peripheral lung. In addition, multiple windows and levels are visible simultaneously with the multiplanar reformations (MPR) and maximum or minimum intensity projections (MIP and minIP) tools can be used interactively at the workstation (1) so that radiologists can trace the whole course of the pulmonary artery and differentiate the relationships between the pulmonary artery and the lung lesion more accurately than conventional CT, even in the peripheral small nodule.
The aim of this study was to evaluate the ability of the relationships between the pulmonary artery and lung lesion, including encasement, displacement, and penetration in distinguishing benign from malignant lung lesion and the degree of pulmonary arterial encasement in predicting malignancy is evaluated with receiver operating characteristic (ROC) curve.
37
Materials and Methods Patients and CT imaging
From June 2005 to December 2005, a total of 100 patients with solitary pulmonary nodule or mass underwent 16-slice MDCT study. There were 69 men and 31 women (age 64.5 ± 15 years old). The final diagnoses were proven and they either underwent transthoracic needle biopsy or transbronchial biopsy with/without brush and wash or thoracotomy or sputum culture and transbronchial lavage culture with follow up (Table 1). Their CT images were performed with two 16-detector row computed tomographies (LightSpeed and BrightSpeed, General Electric Medical Systems). Before dynamic CT was performed, HRCT images were obtained. One hundred mL of iodinated contrast medium was intravenously injected with a power injector at a rate of 3 mL/sec.
The scanning was performed from the lung bases to the middle pole of both kidneys. Smart preparation technique, scanning delay was automatically determinedwith bolus tracking in the aorta, after contrast medium injection and waiting for the density of aorta over than 120 Hu, then starting scan, was used and the ROI (region of interest) was placed in the aortic arch. The scanning parameters were a collimation of 1.25 mm, a table speed of 34.375 mm/sec and a pitch of 1.375. Axial slices were reconstructed with a slice width of 5.0 mm and slice interval of 5.0 mm. Then the 0.625 mm reconstructed raw data of dynamic CT images were sent to the CT workstation (Advantage window 4.4).
Table 1. Methods to prove final diagnosis
Methods to prove final diagnosis Case Numbers
Malignancy 77
Ultrasonography guided biopsy 10 CT* guided biopsy 3 Transbronchial biopsy 41 Transbronchial brush 33 Transbronchial wash 33
Thoracotomy 14
Benignancy 23
CT* guided biopsy 2 Transbronchial wash culture 4
Thoracotomy 4
Sputum culture and F/U** 13
* CT: Computed tomography
** F/U: Follow up until the lesion resolve or stable (about 6-18 months)
Image viewing
A chest radiologist (P-P Tsai-observer 1) with 11 years of experience in chest CT and a chief resident (J-N Shu-observer 2) reviewed the near isotropic data set consists of 300-400 reconstructed CT images at the workstation independently.
39
final diagnosis of each lung lesion. Several tools were used at the workstation to display data and most often MPR and MIP were used in our study. Rotation around and along any axis in real time were also used.
They assessed the relationship of the lung lesions and adjacent pulmonary artery with multiple windows and levels simultaneously at CT workstation and recorded the relationships as encasement, displacement, penetration, in the margin and disconnection. The definition of encasement is mass envelops the pulmonary artery and with decrease the size of caliber (Fig 1). Displacement is indicating mass causes deviation of pulmonary artery away from the normal vascular course with/without notch on pulmonary artery (Fig 2). Penetration is when the pulmonary artery passes through the lesion without change the vascular course or caliber of pulmonary artery (Fig 3). In the margin is when the pulmonary artery passes across the lesion’s margin but without changing the vascular course or change the caliber (Fig 4). Disconnection is no pulmonary artery contact with the lesion.
Figure 1-1. Encasement
This is an 82 year-old male a mass lesion abut left hilum. He received bronchoscopic biopsy and pathology revealed small cell lung carcinoma.
Coronal (A) and axial (B) sections CT images reveal the main tumor envelops the left segmental pulmonary artery with decrease the diameter of this artery (white arrows).
A B
41
Figure 1-2. Amputation
This is a 68 year-old male with small cell lung carcinoma proved by bronchoscopic wash and brush. The main tumor encases the left pulmonary artery (curve arrow) and pulmonary vein (arrow head).
Besides, the blood supply from the left bronchial artery (arrow) is also noted.
Figure 2. Displacement
This is a 68 year-old female with a single pulmonary nodule in right lower lobe. She received right lower lobe lobectomy and pathology revealed
adenocarcinoma. Coronal reformat CT image reveals the nodule push the peripheral right pulmonary artery away from its normal vascular course with a smooth indentation on the pulmonary artery (white arrow).
43
Figure 3. Penetration
This is an 64 year-old male with a mass lesion in left lower lobe. He received ultrasonography guided biopsy and pathology revealed
adenocarcinoma. Sagittal reformat CT image reveals the pulmonary artery passes through the lesion without change the vascular course or caliber of the pulmonary artery (black arrow).
Figure 4. In the margin and encasement
This is a 56 year-old male with adenocarcinoma. Sagittal reformat CT image reveals one pulmonary artery passes across the margin of the lesion (white arrow) but 2 smaller branches (black arrows) were encased by the lesion. The
relationship was recorded as encasement to show the most severe mass effect
More than one type of relationships would be recorded if more than one pulmonary artery was in connection with the lesion such as encasement and displacement or penetration and displacement. When the lesion had different
45
mass effect such as in combination with penetration and different degree of encasement to the different pulmonary arteries or different segments of a pulmonary artery, the observers recorded it as encasement to show the most mass effect. As well, the chest radiologist also measured the size of all lesions and recorded the location of the lesion as central or peripheral lesions. Central lesion is the lesion that occurs in the hilar bronchus (main, lobar, or segmental bronchus) while the peripheral lesion occurs below the level of segmental bronchus.
When the result of the same nodule was not the same from these 2 observers, the results from both observer 1 and 2 were presented to a 3rd observer (H-J Chiang, with 30 years of experience in general radiology, especially with regards to intervention radiology) who reviewed the images at the workstation and made the final decision. In addition, as pulmonary arterial encasement was recorded, the degree of encasement was measured by the 3rd observer at the workstation. As different degrees of encasement at a pulmonary artery or the lesion was encased by more than one pulmonary artery, he would repeatedly place the tracer in the all narrowed segments by zooming in on the images, using different thickness of MIP image, checking the tracer in all planes including axial, sagittal and coronal sections and rotation around the tracer at the workstation. Volume rendering (VR) technique was used to evaluate central pulmonary artery to make sure of the maximal diameter of pulmonary artery.
However, VR was not used in peripheral lesions since there is always not
enough tissue contrast to perform a 3-dimensional image study of pulmonary artery. After repeat calculation, he recorded the data showing the most advanced degree of encasement. The degree of encasement was calculated and the methods were listed as Fig 5 depending on how many pulmonary arterial bification within the lesion. When the vessel is encased and has very lightly enhanced and barely visualized that leading to difficult to measurement, it will be recorded as amputation and the degree of encasement is 100%.
Figure 5. (A) A lesion (circle) encased pulmonary artery and the encased
segment doesn’t include a bification. The degree of encasement was determined by the ratio between the luminal diameter at the point of greatest stenosis, CD, and the normal artery beyondthe lesion at proximal end, AB. The luminal
A C B E D
F Figure 5 (A)
47
Figure 5. (B) A lesion (circle) encased pulmonary artery and the encased segment includes a bification, the narrowest segment was proximal to the bification. The degree of encasement = (1-CD/AB)*100%.
The luminal diameter at the point of greatest stenosis was CD, and the normal artery beyond the lesion at proximal end was AB, at distal end was EF.
The degree of encasement = (1-CD/AB)*100%.
A C B E D
F Figure 5 (B)
Figure 5. (C) A lesion (circle) encased pulmonary artery and the encased
segment includes a bification, the narrowest segment was distal to the bification.
The luminal diameter at the point of greatest stenosis was CD, and the normal artery beyond the lesion at proximal end was AB, at distal end was EF.
The degree of encasement = (1-CD/EF)*100%.
A B
C D E F Figure 5 (C)
49
Figure 5. (D) A lesion (circle) encased pulmonary artery and the encased
segment includes at least 2 bifications. The narrowest point was at the segment between 2 bifications. The degree of encasement = (1-CD/CD’)*100%, CD’=
EF+EC/EA*(AB-EF); CD’ was an approximation of an expected normal
diameter of the narrowest segment. The luminal diameter at the point of greatest stenosis was CD, and the normal artery beyond the lesion at proximal end was AB, at distal end was EF. EC was the distance between the narrowest point to the normal segment beyond the lesion at distal end. EA was the distance of the vessel at normal segments between both ends of the lesion.
Correlation of the pathology and the relationships
Correlation the pathology findings of vascular invasion and the relationship of pulmonary arteries to lung lesions were performed according to the final results
A B
C D
E F Figure 5 (D)
from all the observers and the report of the pathology of the excised malignancies. The pathology staging report was performed according to the American College of chest Physicians (ACCP) evidence-based clinical practice guidelines (9).
Statistical analyses
Statistical analyses were performed with SAS software (version 9.13; SAS Institute, Cary, NC). When a lesion disconnect with all the pulmonary arteries, it would not be included into statistical analysis since we could not evaluate the mass effect from the lesion to the pulmonary artery. Also, when the pulmonary artery was just passing through the margin of lesion and no other pulmonary artery was connected with the lesion, the mass effect from the lesion was not certain. Therefore, it was also not be analyzed.
Statistical analyses were performed with SAS software (version 9.13; SAS Institute, Cary, NC). When a lesion disconnect with all the pulmonary arteries, it would not be included into statistical analysis since we could not evaluate the mass effect from the lesion to the pulmonary artery. Also, when the pulmonary artery was just passing through the margin of lesion and no other pulmonary artery was connected with the lesion, the mass effect from the lesion was not certain. Therefore, it was also not be analyzed.