Probability of cancer in pulmonary nodules detected on first screening CT.

BACKGROUND: Major issues in the implementation of screening for lung cancer by means of low-dose computed tomography (CT) are the definition of a positive result and the management of lung nodules detected on the scans. We conducted a population-based prospective study to determine factors predicting the probability that lung nodules detected on the first screening low-dose CT scans are malignant or will be found to be malignant on follow-up. METHODS: We analyzed data from two cohorts of participants undergoing low-dose CT screening. The development data set included participants in the Pan-Canadian Early Detection of Lung Cancer Study (PanCan). The validation data set included participants involved in chemoprevention trials at the British Columbia Cancer Agency (BCCA), sponsored by the U.S. National Cancer Institute. The final outcomes of all nodules of any size that were detected on baseline low-dose CT scans were tracked. Parsimonious and fuller multivariable logistic-regression models were prepared to estimate the probability of lung cancer. RESULTS: In the PanCan data set, 1871 persons had 7008 nodules, of which 102 were malignant, and in the BCCA data set, 1090 persons had 5021 nodules, of which 42 were malignant. Among persons with nodules, the rates of cancer in the two data sets were 5.5% and 3.7%, respectively. Predictors of cancer in the model included older age, female sex, family history of lung cancer, emphysema, larger nodule size, location of the nodule in the upper lobe, part-solid nodule type, lower nodule count, and spiculation. Our final parsimonious and full models showed excellent discrimination and calibration, with areas under the receiver-operating-characteristic curve of more than 0.90, even for nodules that were 10 mm or smaller in the validation set. CONCLUSIONS: Predictive tools based on patient and nodule characteristics can be used to accurately estimate the probability that lung nodules detected on baseline screening low-dose CT scans are malignant. (Funded by the Terry Fox Research Institute and others; ClinicalTrials.gov number, NCT00751660.).

Plasma pro-surfactant protein B and lung function decline in smokers.

Plasma pro-surfactant protein B (pro-SFTPB) levels have recently been shown to predict the development of lung cancer in current and ex-smokers, but the ability of pro-SFTPB to predict measures of chronic obstructive pulmonary disease (COPD) severity is unknown. We evaluated the performance characteristics of pro-SFTPB as a biomarker of lung function decline in a population of current and ex-smokers. Plasma pro-SFTPB levels were measured in 2503 current and ex-smokers enrolled in the Pan-Canadian Early Detection of Lung Cancer Study. Linear regression was performed to determine the relationship of pro-SFTPB levels to changes in forced expiratory volume in 1 s (FEV1) over a 2-year period as well as to baseline FEV1 and the burden of emphysema observed in computed tomography (CT) scans. Plasma pro-SFTPB levels were inversely related to both FEV1 % predicted (p=0.024) and FEV1/forced vital capacity (FVC) (p<0.001), and were positively related to the burden of emphysema on CT scans (p<0.001). Higher plasma pro-SFTPB levels were also associated with a more rapid decline in FEV1 at 1 year (p=0.024) and over 2 years of follow-up (p=0.004). Higher plasma pro-SFTPB levels are associated with increased severity of airflow limitation and accelerated decline in lung function. Pro-SFTPB is a promising biomarker for COPD severity and progression.

The Lung Reporting and Data System (LU-RADS): a proposal for computed tomography screening.

Despite the positive outcome of the recent randomized trial of computed tomography (CT) screening for lung cancer, substantial implementation challenges remain, including the clear reporting of relative risk and suggested workup of screen-detected nodules. Based on current literature, we propose a 6-level Lung-Reporting and Data System (LU-RADS) that classifies screening CTs by the nodule with the highest malignancy risk. As the LU-RADS level increases, the risk of malignancy increases. The LU-RADS level is linked directly to suggested follow-up pathways. Compared with current narrative reporting, this structure should improve communication with patients and clinicians, and provide a data collection framework to facilitate screening program evaluation and radiologist training. In overview, category 1 includes CTs with no nodules and returns the subject to routine screening. Category 2 scans harbor minimal risk, including <5 mm, perifissural, or long-term stable nodules that require no further workup before the next routine screening CT. Category 3 scans contain indeterminate nodules and require CT follow up with the interval dependent on nodule size (small [5-9 mm] or large [≥ 10 mm] and possibly transient). Category 4 scans are suspicious and are subdivided into 4A, low risk of malignancy; 4B, likely low-grade adenocarcinoma; and 4C, likely malignant. The 4B and 4C nodules have a high likelihood of neoplasm simply based on screening CT features, even if positron emission tomography, needle biopsy, and/or bronchoscopy are negative. Category 5 nodules demonstrate frankly malignant behavior on screening CT, and category 6 scans contain tissue-proven malignancies.

Association of two BRM promoter polymorphisms with head and neck squamous cell carcinoma risk.

The SWI/SNF chromatin remodeling complex is an important regulator of gene expression that has been linked to cancer development. Expression of Brahma (BRM), a critical catalytic subunit of SWI/SNF, is lost in a variety of solid tumors. Two novel BRM promoter polymorphisms (BRM-741 and BRM-1321) have been correlated with BRM loss and elevated cancer risk. The aim(s) of this study were to examine BRM expression in head and neck squamous cell carcinoma (HNSCC) and to correlate BRM polymorphisms with HNSCC risk. BRM expression studies were performed on eight HNSCC cell lines and 76 surgically resected tumor samples. A case-control study was conducted on 668 HNSCC patients (oral cavity, oropharynx, larynx and hypopharynx) and 700 healthy matched controls. BRM expression was lost in 25% of cell lines and 16% of tumors. The homozygous genotype of each polymorphism was significantly associated with increased HNSCC risk [BRM-741: adjusted odds ratio (aOR) 1.75, 95% CI 1.2-2.3, P < 0.001; BRM-1321: aOR 1.65, 95% CI 1.2-2.2, P < 0.001]. Individuals that were homozygous for both BRM polymorphisms had a more than 2-fold increase in the risk of HNSCC (aOR 2.23, 95% CI 1.5-3.4, P < 0.001). A particularly elevated risk was seen within the oropharynx, human papillomavirus-positive subgroup for carriers of both homozygous variants (aOR 3.09, 95% CI 1.5-6.8, P = 0.004). BRM promoter polymorphisms appear to act as susceptibility markers of HNSCC with potential utility in screening, prevention and treatment.

Restrictive allograft syndrome post lung transplantation is characterized by pleuroparenchymal fibroelastosis.

We previously described restrictive allograft syndrome as a form of chronic lung allograft dysfunction, demonstrating restrictive pulmonary function decline. However, the histopathological correlates of restrictive allograft syndrome have yet to be satisfactorily described. We hypothesized that pulmonary pleuroparenchymal fibroelastosis, as has recently been described in bone marrow transplant recipients, may also be present in the lungs of patients with restrictive allograft syndrome. Retrospective review of 493 patients who underwent lung transplantation between 1 January 1996 and 30 June 2009, was conducted. Out of 47 patients with clinical features of restrictive allograft syndrome, 16 had wedge biopsy, re-transplant lung explant, or autopsy lung specimens available for review. All lungs showed varying degrees of pleural fibrosis. Fifteen of 16 showed parenchymal fibroelastosis, characterized by hypocellular collagen deposition with preservation and thickening of the underlying alveolar septal elastic network. The fibroelastosis was predominantly subpleural in distribution, with some cases also showing centrilobular and paraseptal distribution. A sharp demarcation was often seen between areas of fibroelastosis and unaffected lung parenchyma, with fibroblastic foci often present at this interface. Concurrent features of obliterative bronchiolitis were present in 14 cases. Another common finding was the presence of diffuse alveolar damage (13 cases), usually in specimens obtained <1 year after clinical onset of restrictive allograft syndrome. The single specimen in which fibroelastosis was not identified was obtained before the clinical onset of chronic lung allograft dysfunction, and showed features of diffuse alveolar damage. In conclusion, pleuroparenchymal fibroelastosis is a major histopathologic correlate of restrictive allograft syndrome, and was often found concurrently with diffuse alveolar damage. Our findings support a temporal sequence of diffuse alveolar damage followed by the development of pleuroparenchymal fibroelastosis in the histopathologic evolution of restrictive allograft syndrome.

Low-dose computed tomography (LDCT) in workers previously exposed to asbestos: detection of parenchymal lung disease.

OBJECTIVES: To evaluate the lungs of asymptomatic asbestos-exposed workers who were screened for lung cancer and mesothelioma using low-dose computed tomography (LDCT) for parenchymal abnormalities. METHODS: Three hundred fifteen baseline LDCT studies of the chest of participants with at least 20 years' exposure to asbestos or presence of pleural plaques before enrollment on chest radiographs were analyzed. RESULTS: Three hundred fifteen subjects were studied. The mean age was 61.7 years, and the mean exposure to asbestos was 26.9 years. One hundred seventy-five (56%) participants had absence of parenchymal findings with a mean age of 58.7 years, mean exposure of 24.6 years, and a mean smoking pack years of 19. One hundred forty subjects (44%) had parenchymal findings (138 men and 2 women) with a mean age of 65.3 years, mean exposure of 29.73 years, and a mean smoking pack years of 21.5 years. Participants who had parenchymal manifestations were more likely to be older and have longer exposure to asbestos compared to participants who had no relevant parenchymal findings. There was no statistical difference in the mean smoking pack years between the groups with and without parenchymal findings. CONCLUSIONS: Low-dose CT could demonstrate parenchymal lung manifestations in this higher-risk asymptomatic group with prior exposure to asbestos in the setting of screening for lung cancer and mesothelioma. Individuals with longer exposure to asbestos and of higher age have more pulmonary abnormalities. The age and the latency of exposure play an important role given that the asbestos-related parenchymal abnormalities on LDCT were more prevalent in the elderly participants and with longer periods of exposure.

CT screening for lung cancer: implication of lung biopsy recommendations.

OBJECTIVE: The purpose of this article is to address the implications of invasive diagnostic procedures recommended by a lung cancer screening protocol. In particular, we assess how many invasive procedures were recommended for benign nodules. MATERIALS AND METHODS: Between 2003 and 2009, 4782 high-risk current and former smokers were enrolled in a lung cancer screening study. A helical low-dose CT of the chest was performed. Morphologic features targeted were parenchymal nodules. The indication for biopsy was made according to the diagnostic algorithm provided by the International Early Lung Cancer Action Program. We recorded the time points of biopsy recommendation; shape, size, and growth of nodules; types of diagnostic procedures; complication rates; and final pathologic diagnosis. RESULTS: A total of 128 diagnostic biopsies were recommended for suspicious nodules, and 127 biopsies were performed, including 110 percutaneous CT-guided fine-needle aspiration biopsies (FNABs), nine video-assisted thoracoscopic surgery (VATS) resections, seven bronchoscopies, and one ultrasound-guided biopsy of a lymph node. Of 110 FNABs, 24 had unsatisfactory results, 13 of which were referred for secondary diagnostic VATS resection. The indication for biopsy was made on the basis of shape in 48% of cases (62/128), growth on follow-up in 40% of cases (51/128), and the appearance of new nodules in 12% of cases (15/128). In total, 104 of 124 biopsies (84%) were correctly indicated (true-positive recommendation) for malignancy, 20 were benign (false-positive) (16%), and final results are pending for four cases. The overall false-positive recommendation rate was 0.42% (20/4782); 11.6% of FNABs (16/128) and 3.6% of VATS (5/128) revealed benign nodules, corresponding to an overall false-positive rate of 0.33% for FNAB (16/4782) and 0.10% for VATS (5/4782). CONCLUSION: The recommended biopsy procedures for screen-detected suspicious pulmonary nodules resulted in a low intervention rate for benign nodules. This rate is minimal when we followed a research protocol that relies on shape and growth.

Lung cancer associated with cystic airspaces.

OBJECTIVE: The objectives of this study were to determine the frequency of lung cancers associated with a discrete cystic airspace and to characterize the morphologic and pathologic features of the cancer and the cystic airspace. MATERIALS AND METHODS: We reviewed all diagnosed cases of lung cancer resulting from baseline screening (n=595) and annual screening (n=111) in the International Early Lung Cancer Action Program to identify those abutting or in the wall of a cystic airspace. We also reviewed the pathologic specimens. RESULTS: A total of 26 lung cancers were identified abutting or in the wall of a cystic airspace. Of these, 13 were identified at baseline (13/595, 2%) and 13 at annual screening (13/111, 12%), which was significant (p<0.0001). The median circumferential portion of wall involved was less for the annual cancers than for the baseline ones, but this difference did not reach significance (90° vs 240°, p=0.07). The diagnosis was adenocarcinoma in all but three cases. Histologic analysis showed that the cystic space was a bulla, a fibrous walled cyst without a defined lining, or a pleural bleb and that in all but one case, the tumor was eccentric relative to the airspace and the wall of the airspace was unevenly thickened. CONCLUSION: At annual repeat CT screening, the finding of an isolated cystic airspace with increased wall thickness should raise the suspicion of lung cancer.

Repeated low-dose computed tomography in current and former smokers for quantification of emphysema.

OBJECTIVE: To quantify different emphysema evolution in current and former smokers. METHODS: We retrospectively analyzed low-dose computed tomography scans from a lung cancer screening study of 59 current and 75 former smokers. The quantitative emphysema analysis was performed using a home-built software (YACTA version 0.9), yielding the parameters lung volume, emphysema volume (EV), emphysema index (EI), mean lung density, and 15th percentile. RESULTS: The baseline EV and EI were significantly different (median EVformer =422 mL vs EVcurrent =249 mL, P = 0.0003; and median EIformer =7.6 % vs EIcurrent =4.1 %, P = 0.0001, respectively). On the annual repeat scan, the median EI and EV for former smokers had decreased significantly (ΔEIformer = -0.257%, P = 0.004; and ΔEVcurrent = -0.203 mL, P = 0.020), whereas there was no emphysema change in current smokers. CONCLUSIONS: We were able to demonstrate different emphysema evolution in current versus former smokers; emphysema parameters decreased in the former smokers and remained stable in current smokers.

Imaging the diaphragm.

This article describes the normal and abnormal position, motion and morphology of the diaphragm, on chest radiography and fluoroscopy, as well as on computed tomography and magnetic resonance imaging.

Computer-aided detection for the identification of pulmonary nodules in pediatric oncology patients: initial experience.

BACKGROUND: Computer-aided detection (CAD) has been shown to increase the sensitivity for detection of pulmonary nodules in adults. This study reports initial findings utilizing a CAD system for the detection of pediatric pulmonary nodules. OBJECTIVE: To assess the performance of CAD and pediatric radiologists in the detection of pediatric pulmonary nodules. MATERIALS AND METHODS: CT scans from a series of pediatric patients with known primary tumors and lung nodules were analyzed by four radiologists and a commercially available CAD system. IRB approval was obtained. Sensitivities were calculated for detection according to nodule size and location. RESULTS: In 24 children (age 3-18 years) 173 nodules were identified. Overall the sensitivity of CAD was 34%, but the sensitivity of CAD for detection of nodules 4.0 mm or larger was 80%. Overall radiologist sensitivity ranged from 68% to 79%. There were 0.9 CAD false-positives and 0.3-2.4 radiologist false-positives per study. CONCLUSION: CAD in our pediatric oncology patients had good sensitivity for detection of lung nodules 4 mm and larger with a low number of false-positives. However, the sensitivity was considerably less for nodules smaller than 4 mm.

Computed tomography perfusion using first pass methods for lung nodule characterization.

OBJECTIVE: To evaluate computed tomography (CT) perfusion using first pass methods for lung nodule characterization. METHODS: Fifty-seven patients with 51 malignant and 6 benign nodules underwent first-pass, dynamic contrast-enhanced-CT (50 mL, 3-5 mL/s.). Kinetic analysis tools were CT Perfusion 3 (GEMS, Milwaukee, WI), a distributed parameter model approach, yielding blood volume (BV; mL/100 g), blood flow (BF; mL/min/100 g), mean transit time (1/s), and permeability surface area (mL/min/100 g), and an in-house Patlak-style analysis yielding fractional BV (mL/100 g) and an estimate of extraction (Kps, mL/100 g/min). RESULTS: CT Perfusion 3 parameters in malignant and benign nodules were: mean transit time 10.1 +/- 0.9 1/s versus 11.1 +/- 3.1 1/s (ns), permeability surface 23.3 +/- 9.1 mL/min/100 g versus 19.6 +/- 10.3 mL/min/100 g (ns), BF 111.3 +/- 8.7 mL/min/100 g versus 39.1+/- 5.7 mL/min/100 g (P < 0.001), BV 9.3+/- 0.7 mL/100 g versus 4.1 +/- 1.1 mL/100 g (P < 0.002); Patlak parameters were: Kps 13.3 +/- 1.2 mL/100 g/min versus 3.9 +/- 0.8 mL/100 g/min (P < 0.001), BV 8.4 +/- 0.8 mL/100 g versus 3.6 +/- 1.3 mL/100 g (P < 0.01). The two kinetic methods show good agreement for BV estimation (Bland-Altman plot). The limits of agreement (bias +/-2 standard deviation of bias) were 1.2 +/- 5.3 mL/100 g. CONCLUSION: CT Perfusion using first pass modeling appears feasible for lung nodule characterization. Given the short acquisition duration used, weaknesses of the modeling methods are exposed. Nonetheless, microvascular characterization in terms of BF, BV, or Kps appears useful in distinguishing malignant from benign nodules.

Radiology resident interpretation of on-call CT pulmonary angiograms.

RATIONALE AND OBJECTIVES: To evaluate the interpretation of computed tomographic pulmonary angiograms performed outside of regular reporting hours, comparing the initial interpretation by the radiology resident to the attending radiologist. MATERIALS AND METHODS: Records for 840 consecutive computed tomographic pulmonary angiograms (CTPA) performed outside of regular reporting hours at two tertiary referral centers from January 1, 2004-December 31, 2005 were reviewed. The preliminary interpretation by the on-call radiology resident was compared to the subsequent final report issued by a subspecialty trained chest radiologist. Studies were stratified as positive, negative, or equivocal for pulmonary embolus. Cases with discordant interpretations or negative CTPA were reviewed to determine impact on clinical outcome. Patients were followed up to 12 months after CTPA to document any subsequent thromboembolic event. RESULTS: Sixteen percent (131/840) of CTPAs were reported positive by the staff radiologist. There was agreement in 90% (752/840) of studies (P = .76, 95% confidence interval, 0.71-0.81) with 86% (114/133) agreement for studies interpreted as positive by residents, 95% (582/612) for studies interpreted as negative by residents, and 63% (60/95) for studies interpreted as equivocal by residents. Studies of optimal quality had higher interobserver agreement than studies of suboptimal quality (P < .0001). In-patient studies were more likely to be positive than emergency room patients (20% vs. 13%) (P = .004). No adverse clinical outcomes were attributed to discordant interpretations. CONCLUSIONS: Radiology residents provide a high level interpretation of on-call CTPA studies, achieving good concordance with the attending radiologists' assessment.

The use of computer-aided detection for the assessment of pulmonary arterial filling defects at computed tomographic angiography.

PURPOSE: To validate a computer-aided detection (CAD) tool for the detection of pulmonary arterial filling defects at computed tomographic pulmonary angiography (CTPA) and to assess its benefit for readers of different levels of experience. METHODS: One hundred consecutive CTPA studies were retrospectively evaluated by a chest radiologist for presence of emboli, serving as the reference standard. Subsequently, examinations were analyzed using commercially available second-generation CAD software (ImageChecker CT, version 2.1; R2 Technology, Inc., Sunnyvale, Calif). The staff radiologist assessed all CAD marks and classified them as true positive or false positive (FP), and any unmarked emboli were classified as false negative. Computer-aided detection software was also evaluated on a case basis compared with the reference standard.For the second part of the study, the 100 CTPAs were reviewed by 3 additional readers of different levels of experience, both without and with CAD, and findings correlated with the reference standard. RESULTS: Twenty-one studies (21%) were positive for pulmonary embolism. Of these, 18 were true positive on a case basis, and 3 were false negative. Of the 79 negative studies, 16 were true negative with no CAD marks, and the remaining 63 were FP. On a case basis, CAD sensitivity was 86%, specificity was 20%, negative predictive value was 84%, and positive predictive value (PPV) was 22%.Overall, the CAD software yielded 318 marks, identifying 64 of 93 emboli with an additional 254 FP marks. On a mark basis, sensitivity was 69%, and PPV was 20%.Computer-aided detection did not influence the most experienced reader (a chest fellow). Although CAD improved the subjective confidence of the second-year resident in some cases, it had no influence on overall interpretation or accuracy. Computer-aided detection improved accuracy only for the most inexperienced reader, helping this reader to identify 9 emboli not initially appreciated. CONCLUSIONS: Computer-aided detection specificity and PPV are poor due to expected FP marks, although, often, these can be easily dismissed. However, CAD software may play an important role as a second reader for residents or inexperienced readers.

A comparison of recognition performances in speech-spectrum noise by listeners with normal hearing on PB-50, CID W-22, NU-6, W-1 spondaic words, and monosyllabic digits spoken by the same speaker.

BACKGROUND: So that portions of the classic Miller, Heise, and Lichten (1951) study could be replicated, new recorded versions of the words and digits were made because none of the three common monosyllabic word lists (PAL PB-50, CID W-22, and NU-6) contained the 9 monosyllabic digits (1-10, excluding 7) that were used by Miller et al. It is well established that different psychometric characteristics have been observed for different lists and even for the same materials spoken by different speakers. The decision was made to record four lists of each of the three monosyllabic word sets, the monosyllabic digits not included in the three sets of word lists, and the CID W-1 spondaic words. A professional female speaker with a General American dialect recorded the materials during four recording sessions within a 2-week interval. The recording order of the 582 words was random. PURPOSE: To determine-on listeners with normal hearing-the psychometric properties materials presented in speech-spectrum noise. RESEARCH DESIGN: A quasi-experimental, repeated-measures design was used. STUDY SAMPLE: Twenty-four young adult listeners (M = 23 years) with normal pure-tone thresholds (< or = 20-dB HL at 250 to 8000 Hz) participated. The participants were university students who were unfamiliar with the test materials. DATA COLLECTION AND ANALYSIS: The 582 words were presented at four signal-to-noise ratios (SNRs; -7-, -2-, 3-, and 8-dB) in speech-spectrum noise fixed at 72-dB SPL. Although the main metric of interest was the 50% point on the function for each word established with the Spearman-Kärber equation (Finney, 1952), the percentage correct on each word at each SNR was evaluated. The psychometric characteristics of the PB-50, CID W-22, and NU-6 monosyllabic word lists were compared with one another, with the CID W-1 spondaic words, and with the 9 monosyllabic digits. RESULTS: Recognition performance on the four lists within each of the three monosyllabic word materials were equivalent, +/- 0.4 dB. Likewise, word-recognition performance on the PB-50, W-22, and NU-6 word lists were equivalent, +/- 0.2 dB. The mean recognition performance at the 50% point with the 36 W-1 spondaic words was approximately 6.2 dB lower than the 50% point with the monosyllabic words. Recognition performance on the monosyllabic digits was 1-2 dB better than mean performance on the monosyllabic words. CONCLUSIONS: Word-recognition performances on the three sets of materials (PB-50, CID W-22, and NU-6) were equivalent, as were the performances on the four lists that make up each of the three materials. Phonetic/phonemic balance does not appear to be an important consideration in the compilation of word-recognition lists used to evaluate the ability of listeners to understand speech. A companion paper examines the acoustic, phonetic/phonological, and lexical variables that may predict the relative ease or difficulty for which these monosyllable words were recognized in noise (McArdle and Wilson, this issue).

Carotid stent delivery in an XMR suite: immediate assessment of the physiologic impact of extracranial revascularization.

BACKGROUND AND PURPOSE: Patients undergoing stent placement as treatment for severe stenosis of the internal carotid artery (ICA) were assessed with MR imaging in a combined MR-radiographic (XMR) angiography suite. MR imaging was performed before and immediately following conventional radiography-guided stent placement. Changes in MR imaging measurable properties, including flow and perfusion, resulting from stent placement were evaluated. PATIENTS AND TECHNIQUES: MR imaging analysis was performed for 12 patients with >70% stenosis of the ICA before and after conventional radiography-guided deployment of a carotid stent. MR imaging acquisitions included angiography, quantitative flow analysis, perfusion, diffusion, and turbo-fluid-attenuated inversion recovery (FLAIR). These acquisitions were all performed immediately before and following stent placement by using conventional techniques. RESULTS: MR angiography proved sufficient for identifying the target lesion and permitting targeted flow analysis. MR flow analysis demonstrated a marked increase in flow in the treated carotid artery (+2.2 +/- 1.2 mL/s) and little change in other extracranial arteries. MR perfusion imaging showed no significant differences in relative cerebral blood volume between hemispheres before or after treatment, but there was a modest decrease in mean transit time and time to peak evident in the treated hemisphere after stent placement. Diffusion imaging did not demonstrate any ischemic foci resulting from carotid stent treatment. Hyperintensity of the CSF was noted on turbo-FLAIR acquisitions in the ipsilateral hemisphere following stent placement in 75% of patients. CONCLUSION: MR imaging reliably reflects the state of the carotid artery and provides a means of monitoring and quantifying the effects of revascularization.

Retrospective Analysis of Lung Transplant Recipients Found to Have Unexpected Lung Cancer in Explanted Lungs.

Unexpected lung cancer is sometimes found in explanted lungs. The objective of this study was to review these patients and their outcomes to better understand and optimize management protocols for lung transplant candidates with pulmonary nodules. Retrospective analysis of pretransplant imaging and clinicopathologic characteristics of patients who were found to have lung cancer in their explanted lungs was performed. From January 2003 to December 2012, 13 of 853 lung transplant recipients were found to have unexpected lung cancer in their explanted lung (1.52%). Of them, 9 cases were for interstitial lung disease (2.8%; 9/321 recipients) and 4 cases were for chronic obstructive pulmonary disease (1.57%; 4/255 recipients). The median period between computed tomographic scan and lung transplantation was 2.40 months (range: 0.5-19.2). On computed tomographic scan, only 3 cases were shown to possibly have a neoplasm by the radiologist. The staging of these lung cancers was as follows: 3 cases of IA, 1 case of IB, 5 cases of IIA, 1 case of IIIA, and 3 cases of IV. Of 13 cases, 9 died owing to cancer progression. On the contrary, only 1 stage I case with small cell lung cancer showed cancer recurrence. The median survival time was 339 days, and the 3-year survival rate was 11.0%. In conclusion, most of the patients with unexpected lung cancer showed poor prognosis except for the early-stage disease. The establishment of proper protocol for management of such nodules is important to improve the management of candidates who are found to have pulmonary nodules on imaging.

Classification and Reporting of Late Radiographic Changes After Lung Stereotactic Body Radiotherapy: Proposing a New System.

UNLABELLED: Radiation-induced parenchymal lung changes after stereotactic body radiotherapy are common, and can obscure the primary tumor site. In this study we propose a structured radiographic reporting tool for characterization of these changes, pilot its feasibility in a group of radiation oncologists, and test the interrater agreement. We could demonstrate the applicability of the scale, with a fair to moderate agreement. BACKGROUND: The purpose of the study was to design and pilot a synoptic scale for characterization of late radiographic changes after lung stereotactic body radiotherapy (SBRT). PATIENTS AND METHODS: A participatory design process involving 6 radiation oncologists and 2 thoracic radiologists was used in the scale's design. Seventy-seven early-stage non-small-cell lung cancer patients who were treated with SBRT were included, and after treatment their serial computed tomography (CT) images were scored by 6 radiation oncologists. Gwet's First-order Agreement Coefficient (AC1) and a leave-one-out (LOO) analysis was used to assess interrater reliability and variability among raters, respectively. RESULTS: The scale reports on 5 independent categories including "tumor in primary site," "tumor in involved lobe," "consolidation," "volume loss," and "ground-glass or interstitial changes." At each time point, each category is reported as "increased," "stable," "decreased," "obscured," or "not present," compared with the previous. The total number of rated images for the pilot ranged from 450 at 6 months to 84 at 48 months. The primary tumor site was scored as obscured in 38% to 40% of ratings from 12 months onward; 3% to 5% of primary tumors were scored as "increased." Consolidation, volume loss, and ground-glass or interstitial changes were increasingly marked as "stable" with time. At 24 months, AC1 was 0.28 (LOO, 0.22-0.42), 0.47 (LOO, 0.39-0.72), 0.45 (LOO, 0.42-0.50), 0.21 (LOO, 0.15-0.26), and 0.25 (LOO, 0.20-0.38) for the 5 categories listed, respectively. CONCLUSION: In a population of clinicians, this scale could be implemented to characterize evolving lung changes after SBRT, and had fair to moderate interrater agreement. Obscured tumor site is a common challenge of follow-up CT imaging, and new imaging techniques should be explored. This scale provides a tool for communicating changes after SBRT.

Trial design and reporting standards for intra-arterial cerebral thrombolysis for acute ischemic stroke.

BACKGROUND AND PURPOSE: The National Institutes of Health (NIH) estimates that stroke costs now exceed 45 billion dollars per year. Stroke is the third leading cause of death and one of the leading causes of adult disability in North America, Europe, and Asia. A number of well-designed randomized stroke trials and case series have now been reported in the literature to evaluate the safety and efficacy of thrombolytic therapy for the treatment of acute ischemic stroke. These stroke trials have included intravenous studies, intra-arterial studies, and combinations of both, as well as use of mechanical devices for removal of thromboemboli and of neuroprotectant drugs, alone or in combination with thrombolytic therapy. At this time, the only therapy demonstrated to improve outcomes from an acute stroke is thrombolysis of the clot responsible for the ischemic event. There is room for improvement in stroke lysis studies. Divergent criteria, with disparate reporting standards and definitions, have made direct comparisons between stroke trials difficult to compare and contrast in terms of overall patient outcomes and efficacy of treatment. There is a need for more uniform definitions of multiple variables such as collateral flow, degree of recanalization, assessment of perfusion, and infarct size. In addition, there are multiple unanswered questions that require further investigation, in particular, questions as to which patients are best treated with thrombolysis. One of the most important predictors of clinical success is time to treatment, with early treatment of <3 hours for intravenous tissue plasminogen activator and <6 hours for intra-arterial thrombolysis demonstrating significant improvement in terms of 90-day clinical outcome and reduced cerebral hemorrhage. It is possible that improved imaging that identifies the ischemic penumbra and distinguishes it from irreversibly infarcted tissue will more accurately select patients for therapy than duration of symptoms. There are additional problems in the assessment of patients eligible for thrombolysis. These include being able to predict whether a particular site of occlusion can be successfully revascularized, predict an individual patient's prognosis and outcome after revascularization, and in particular, to predict the development of intracerebral hemorrhage, with and without clinical deterioration. It is not clear to assume that achieving immediate flow restoration due to thrombolytic therapy implies clinical success and improved outcome. There is no simple correlation between recanalization and observed clinical benefit in all ischemic stroke patients, because other interactive variables, such as collateral circulation, the ischemic penumbra, lesion location and extent, time to treatment, and hemorrhagic conversion, are all interrelated to outcome. METHODS: This article was written under the auspices of the Technology Assessment Committees for both the American Society of Interventional and Therapeutic Neuroradiology and the Society of Interventional Radiology. The purpose of this document is to provide guidance for the ongoing study design of trials of intra-arterial cerebral thrombolysis in acute ischemic stroke. It serves as a background for the intra-arterial thrombolytic trials in North America and Europe, discusses limitations of thrombolytic therapy, defines predictors for success, and offers the rationale for the different considerations that might be important during the design of a clinical trial for intra-arterial thrombolysis in acute stroke. Included in this guidance document are suggestions for uniform reporting standards for such trials. These definitions and standards are mainly intended for research trials; however, they should also be helpful in clinical practice and applicable to all publications. This article serves to standardize reporting terminology and includes pretreatment assessment, neurologic evaluation with the NIH Stroke Scale score, imaging evaluation, occlusion sites, perfusion grades, follow-up imaging studies, and neurologic assessments. Moreover, previously used and established definitions for patient selection, outcome assessment, and data analysis are provided, with some possible variations on specific end points. This document is therefore targeted to help an investigator to critically review the scales and scores used previously in stroke trials. This article also seeks to standardize patient selection for treatment based on neurologic condition at presentation, baseline imaging studies, and utilization of standardized inclusion/exclusion criteria. It defines outcomes from therapy in phase I, II, and III studies. Statistical approaches are presented for analyzing outcomes from prospective, randomized trials with both primary and secondary variable analysis. A discussion on techniques for angiography, intra-arterial thrombolysis, anticoagulation, adjuvant therapy, and patient management after therapy is given, as well as recommendations for posttreatment evaluation, duration of follow-up, and reporting of disability outcomes. Imaging assessment before and after treatment is given. In the past, noncontrast CT brain scans were used as the initial screening examination of choice to exclude cerebral hemorrhage. However, it is now possible to quantify the volume of early infarct by using contiguous, discrete (nonhelical) images of 5 mm. In addition, CT angiography by helical scanning and 100 mL of intravenous contrast agent can be used expeditiously to obtain excellent vascular anatomy, define the occlusion site, obtain 2D and 3D reformatted vascular images, grade collateral blood flow, and perform tissue-perfusion studies to define transit times of a contrast bolus through specific tissue beds and regions of interest in the brain. Dynamic CT perfusion scans to assess the whole dynamics of a contrast agent transit curve can now be routinely obtained at many hospitals involved in these studies. The rationale, current status of this technology, and potential use in future clinical trials are given. Many hospitals are also performing MR brain studies at baseline in addition to, or instead of, CT scans. MRI has a high sensitivity and specificity for the diagnosis of ischemic stroke in the first several hours from symptom onset, identifies arterial occlusions, and characterizes ischemic pathology noninvasively. Case series have demonstrated and characterized the early detection of intraparenchymal hemorrhage and subarachnoid hemorrhage by MRI. Echo planar images, used for diffusion MRI and, in particular, perfusion MRI are inherently sensitive for the susceptibility changes caused by intraparenchymal blood products. Consequently, MRI has replaced CT to rule out acute hemorrhage in some centers. The rationale and the potential uses of MR scanning are provided. In addition to established criteria, technology is continuously evolving, and imaging techniques have been introduced that offer new insights into the pathophysiology of acute ischemic stroke. For example, a better patient stratification might be possible if CT and/or MRI brain scans are used not only as exclusion criteria but also to provide individual inclusion and exclusion criteria based on tissue physiology. Imaging techniques might also be used as a surrogate outcome measure in future thrombolytic trials. The context of a controlled study is the best environment to validate emerging imaging and treatment techniques. The final section details reporting standards for complications and adverse outcomes; defines serious adverse events, adverse events, and unanticipated adverse events; and describes severity of complications and their relation to treatment groups. Recommendations are made regarding comparing treatment groups, randomization and blinding, intention-to-treat analysis, quality-of-life analysis, and efficacy analysis. This document concludes with an analysis of general costs associated with therapy, a discussion regarding entry criteria, outcome measures, and the variability of assessment of the different stroke scales currently used in the literature is also featured. CONCLUSIONS: In summary, this article serves to provide a more uniform set of criteria for clinical trials and reporting outcomes used in designing stroke trials involving intra-arterial thrombolytic agents, either alone or in combination with other therapies. It is anticipated that by having a more uniform set of reporting standards, more meaningful analysis of the data and the literature will be able to be achieved.