Noncalcified Nodules Research Articles

Low Yield of Chest Radiography in a Large Tuberculosis Screening Program

To assess the frequency and spectrum of abnormalities on routine screening chest radiographs in the pre-employment evaluation of health care workers with positive tuberculin skin test (TST) results. The institutional review board approved this HIPAA-compliant retrospective study and waived the need for written informed patient consent. Chest radiographic reports of all 2586 asymptomatic individuals with positive TST results who underwent pre-employment evaluation between January 1, 2003, and December 31, 2007, were evaluated to determine the frequency of detection of evidence of active tuberculosis (TB) or latent TB infection (LTBI) and the spectrum of imaging findings. All chest radiographs interpreted as positive were reviewed by an experienced board-certified radiologist. If there was a discrepancy between the two readings, a second experienced radiologist served as an independent and final arbiter. Any follow-up chest radiographs or computed tomographic images that had been acquired by employee health services or by the employee's private physician as a result of a suspected abnormality detected at initial screening were also evaluated. Of the 159 (6.1%) chest radiographic examinations that yielded abnormal results, there were no findings that were consistent with active TB. There were 92 cases of calcified granulomas, calcified lymph nodes, or both; 25 cases of apical pleural thickening; 16 cases of fibrous scarring; and 31 cases of noncalcified nodules. All cases of fibrous scarring involved an area smaller than 2 cm(2). All noncalcified nodules were 4 mm in diameter or smaller, with the exception of one primary lung malignancy and one necrotizing granuloma (negative for acid-fast bacilli) that grew Mycobacterium kansasii on culture. Universal chest radiography in a large pre-employment TB screening program was of low yield in the detection of active TB or increased LTBI reactivation risk, and it provided no assistance in deciding which individuals to prioritize for LTBI treatment.

Systemic granulomatous disease and syndrome of inappropriate antidiuretic hormone

A 71-year-old man was admitted with generalized tiredness, mild confusion and low-grade pyrexia following the fourth cycle of intravesical bacillus Calmette–Guérin instillation for the treatment of superficial bladder carcinoma. These symptoms were accompanied by some weight loss which was difficult to quantify. His past medical history included type 1 diabetes mellitus, chronic obstructive pulmonary disease and prostatic hyperplasia. He was a smoker and consumed a moderate amount of alcohol. Physical examination was unremarkable with the exception of confusion (abbreviated mental test score 7/10). Initial investigations showed low serum sodium of 122 mmol/litre with normal potassium, renal and thyroid functions. His liver functions were abnormal with aspartate transferase of 76 IU/litre and alkaline phosphatase 286 U/litre. Chest X-ray showed bilateral non-specific reticular changes suggestive of infection. Two sets of blood cultures showed no growth after 72 hours. Urine tests for legionella and pneumococcal antigen were negative. Computed tomography of the brain revealed deep white matter changes suggestive of small vessel disease. On further investigations urine osmolality was 546 mOsm/kg, serum osmolality 256 mOsm/kg, urine sodium 61 mmol/litre and the short Synacthen test was normal, confirming the diagnosis of syndrome of inappropriate antidiuretic hormone. After fluid restriction to 1 litre per day his sodium level started to improve slowly, but the patient's condition continued to deteriorate with ongoing low-grade pyrexia, confusion and lethargy. A repeat chest X-ray 5 days later (Figure 1) showed multiple small non-calcified nodules in both lungs raising the possibility of miliary tuberculosis. This was confirmed on high resolution computed tomography scan of the chest (Figure 2) as presence of bilateral diffuse miliary shadowing in keeping with a diagnosis of miliary tuberculosis. In view of his confusion, CSF examination was done to rule out CNS involvement, but this was normal. No endobronchial lesions were identified on bronchoscopy and bronchial washings were sent for analysis and cultures. The patient was started on anti-tuberculous treatment (isoniazid, rifampicin and ethambutol) as well as steroids and pyridoxine. Unfortunately, the patient suffered a cardiac arrest and died a week after starting the treatment. Cultures of bronchial lavage and CSF did not grow any mycobacterium. On post-mortem examination he was found to have multiple small whitish nodules in both lungs, with caseating granulomata, central areas of necrosis and multinucleated giant cells microscopically.

Early detection of lung cancers – Comparison of computed tomography, cytology and fuzzy-based tumor markers panels

Lung cancer is still a primary cause of cancer death in the western world. Thus, a comprehensive primary diagnostic program which comprises the measurement of biomarkers released by lung cancers is of great importance in the clinical management of lung cancer patients. This review present data for the early lung cancer detection comparing computed tomography (CT), sputum cytology and a tumor marker panel of CYFRA 21-1, CEA, NSE, ProGRP, and SCC which was included into fuzzy classification.Sensitivities in the CT studies were mainly reported with 100% and in sputum analyses with a maximum of 87.5%. The corresponding specificity in sputum cytology analysis was 92.7%. By use of CT, all peripheral squamous or adenocarcinomas of the lung were detected, but there was a lack in detection of SCLC or central localised tumors. In addition, CT detected many non-calcified nodules, of which only a fraction is actual lung cancer leading to a considerable amount of false positive results. At 95{\%}-specificity the sensitivity of a tumor marker panel included into fuzzy modelling for the detection of NSCLC was 50% at stage I. Also SCLC patients could be detected in more than 70% in limited disease stage. Detection rates of advanced tumor stages were even higher. The positive predictive value of biological markers was 80% while the negative predictive value reached around 90%. Modern biological marker approaches in combination with CT and sputum cytology analyses may improve the differential diagnosis especially for the early detection of lung cancer in high-risk populations.

Evaluation of a method of computer-aided detection (CAD) of pulmonary nodules at computed tomography

The authors sought to compare the sensitivity and reading time obtained using computer-aided detection (CAD) software as second reader (SR) or concurrent reader (CR) in the identification of pulmonary nodules. Unenhanced CT scans of 100 consecutive cancer patients were retrospectively reviewed by four readers to identify all solid, noncalcified pulmonary nodules ranging from 3 to 30 mm in diameter. The sensitivity and reading time of each reader and of CAD alone were calculated at 3-mm and 5-mm thresholds with respect to the reference standard, consisting of a consensus reading by the four radiologists involved in the study. The McNemar test was used to compare the sensitivities obtained by reading without CAD (readers 1 and 2), with CAD as SR (readers 1 and 2 with a 2-month delay), and with CAD as CR (readers 3 and 4). The paired Student's t test was used to compare reading times. A value of p<0.05 was considered statistically significant. A total of 258 and 224 nodules were identified at 3-mm and 5-mm thresholds, respectively. The sensitivity of CAD alone was 62.79% and 67.41% at the 3-mm and 5-mm threshold values respectively, with 4.15 and 2.96 false-positive findings per examination. CAD as SR produced a significant increase in sensitivity (p<0.001) in nodule detection with respect to reading without CAD both at 3 mm (12.01%) and 5 mm (10.04%); the average increase in sensitivity obtained when comparing CAD as SR to CAD as CR was statistically significant (p<0.025) both at the 3-mm (5.35%) and 5-mm (4.68%) thresholds. CAD as CR produced a nonsignificant increase in sensitivity compared with reading without CAD (p>0.05). Mean reading time using CAD as SR (330 s) was significantly longer than reading without CAD (135 s, p<0.001) and reading with CAD as CR (195 s, p<0.025). The use of CAD as CR, without any significant increase in reading time, produces no significant increase in sensitivity in pulmonary nodule detection when compared with reading without CAD (p>0.05); CAD as SR, at the cost of longer reading times, increases sensitivity when compared with reading without CAD (p<0.001) or with CAD as CR (p<0.025).

Baseline results of lung cancer screening program for family lung cancer risk with low-dose spiral CT in Taiwan.

7098 Background: The family history is considered as a risk factor for lung cancer in nonsmokers. The value of surveillance for lung cancer with a family risk has not been established. We conduct the study to evaluate the feasibility of lung cancer screening by low- dose spiral CT (LDCT) in lung cancer families. Methods: The nonrandomized study enrolled family members of lung cancer patients. The criteria limited to family members (1) first-degree relatives had lung cancer (simplex family); two or more relatives with lung cancer (multiplex family), and (2) age older than 55 years. They receive annual CT for three years. The modified Early Lung Cancer Action Project protocol was used for investigation. The incidence of noncalcified nodules and prevalence of lung cancer are primary objects in baseline screening. Results: 1,125 participants from 559 families of lung cancer were recruited between August 2007 and November 2009. 810 patients were from 418 simplex families and 315 came from 141 multiplex families. The mean age of participants was 60.74 (±8.99 SD). 515 (45.8%) patients were male. 71.5% of participants are never smokers. Noncalcified nodules (NCN) were detected in 481 (42.8%) patients. The positive test, defined as NCN > 5 mm was 24.9% (280/1,125). The positive screen rates were not different between simplex and multiplex families (24.8% vs. 25.1% , p=0.927).Biopsies were performed in 35 patients. 19 had lung cancer (13 adenocarcinomas, five bronchoalveolar carcinomas [BAC] and one atypical carcinoid tumor) and 16 showed benign lesions. The stages of non-small cell lung cancer included 11 (IA), one (IB), two (IIA), one (IIIA), and four patients (IV), respectively. The mean size of cancer was 18.9 mm (ranged 9 ∼34 mm). The CT morphologies of lung cancer include eight nonsolid pattern (four adenocarcinomas and fours BACs), five part-solid pattern, and six solid nodules. The 11 of 19 lung cancer patients were female (57.9%). Among the 19 cancer patients, 12 patients (12/315; 3.8%) were from multiplex family and the others (7/810; 0.9%) occurred in simplex family (p =0.001). 78.9% (15/19) patients were never smokers. Conclusions: Our study provides evidence of lung cancer prevalence based on family risk. No significant financial relationships to disclose.

The MAGIC-5 CAD for nodule detection in low dose and thin slice lung CTs

Lung cancer is the leading cause of cancer-related mortality in developed countries. Only 10–15% of all men and women diagnosed with lung cancer live 5 years after the diagnosis. However, the 5-year survival rate for patients diagnosed in the early asymptomatic stage of the disease can reach 70%. Early-stage lung cancers can be diagnosed by detecting non-calcified small pulmonary nodules with computed tomography (CT). Computer-aided detection (CAD) could support radiologists in the analysis of the large amount of noisy images generated in screening programs, where low-dose and thin-slice settings are used. The MAGIC-5 project, funded by the Istituto Nazionale di Fisica Nucleare (INFN, Italy) and Ministero dell’Università e della Ricerca (MUR, Italy), developed a multi-method approach based on three CAD algorithms to be used in parallel with a merging of their results: the Channeler Ant Model (CAM), based on Virtual Ant Colonies, the Dot-Enhancement/Pleura Surface Normals/VBNA (DE-PSN-VBNA), and the Region Growing Volume Plateau (RGVP). Preliminary results show quite good performances, to be improved with the refining of the single algorithm and the added value of the results merging.

Perifissural Nodules Seen at CT Screening for Lung Cancer

To describe and characterize the potential for malignancy of noncalcified lung nodules adjacent to fissures that are often found in current or former heavy smokers who undergo computed tomography (CT) for lung cancer screening. Institutional review board approval and informed consent were obtained. Baseline and follow-up thin-section multidetector CT scans obtained in 146 consecutive subjects at high risk for lung cancer (age range, 50-75 years; > 30 pack-year smoking history) were retrospectively reviewed. Noncalcified nodules (NCNs) were categorized according to location (parenchymal, perifissural), shape, septal connection, manually measured diameter, diameter change, and lung cancer outcome at 7(1/2) years. Retrospective review of images from 146 baseline and 311 follow-up CT examinations revealed 837 NCNs in 128 subjects. Of those 837 nodules, 234 (28%), in 98 subjects, were adjacent to a fissure and thus classified as perifissural nodules (PFNs). Multiple (range, 2-14) PFNs were seen in 47 subjects. Most PFNs were triangular (102/234, 44%) or oval (98/234, 42%), were located inferior to the carina (196/234, 84%), and had a septal connection (171/234, 73%). The mean maximal length was 3.2 mm (range, 1-13 mm). During 2-year follow-up in 71 subjects, seven of 159 PFNs increased in size on one scan but were then stable. The authors searched a lung cancer registry 7(1/2) years after study entry and found 10 lung cancers in 139 of 146 study subjects who underwent complete follow-up; none of these cancers had originated from a PFN. PFNs are frequently seen on screening CT scans obtained in high-risk subjects. Although PFNs may show increased size at follow-up CT, the authors in this study found none that had developed into lung cancer; this suggests that the malignancy potential of PFNs is low. (c) RSNA, 2010.

What to Do with a Pulmonary Nodule

Using computed tomography (CT) to screen for lung cancer creates an inherent problem: what to do when a small, solitary, noncalcified pulmonary nodule

Effects of Vitamin E on the Osteoblast Differentiation

Vitamin E is thought to affect bone formation and bone remodeling. In this study, we investigated the effects of vitamin E (alpha-tocopherol and delta-tocopherol) on the osteoblasts isolated from rat calvariae. At 4 and 7 days (Day 4 and 7) after induction of osteoblastic differentiation, treatment of alpha-tocopherol (100 and 200 microM) and delta-tocopherol (2 and 20 microM) for 3 days significantly decreased alkaline phophatase activity of the cultured osteoblasts. At Day 14, however, no significant change was detected in ALP activity and expression of bone sialoprotein mRNA in the osteoblasts treated with alpha-tocopherol or delta-tocopherol for 3 days. Expression of osteocalcin mRNA was decreased by treatment of alpha-tocopherol (100 and 200 microM) and delta-tocopherol (2 and 20 microM) at Day 4 and 7. At Day 14, expression of osteocalcin mRNA was decreased only with treatment of 200 microM alpha-tocopherol. In addition, the noncalcified nodules were decreased by treatment of alpha-tocopherol (200 microM) and delta-tocopherol (20 microM) at Day 7. However, treatment of alpha-tocopherol and delta-tocopherol showed no significant change of formation of calcified nodules at Day 14. These results indicate that vitamin E inhibits differentiation of osteoblasts especially from early stage to osteoid-producing stage.

Management of Lung Nodules Detected by Volume CT Scanning

The use of multidetector computed tomography (CT) in lung-cancer screening trials involving subjects with an increased risk of lung cancer has highlighted the problem for the clinician of deciding on the best course of action when noncalcified pulmonary nodules are detected by CT. A total of 7557 participants underwent CT screening in years 1, 2, and 4 of a randomized trial of lung-cancer screening. We used software to evaluate a noncalcified nodule according to its volume or volume-doubling time. Growth was defined as an increase in volume of at least 25% between two scans. The first-round screening test was considered to be negative if the volume of a nodule was less than 50 mm(3), if it was 50 to 500 mm(3) but had not grown by the time of the 3-month follow-up CT, or if, in the case of those that had grown, the volume-doubling time was 400 days or more. In the first and second rounds of screening, 2.6% and 1.8% of the participants, respectively, had a positive test result. In round one, the sensitivity of the screen was 94.6% (95% confidence interval [CI], 86.5 to 98.0) and the negative predictive value 99.9% (95% CI, 99.9 to 100.0). In the 7361 subjects with a negative screening result in round one, 20 lung cancers were detected after 2 years of follow-up. Among subjects at high risk for lung cancer who were screened in three rounds of CT scanning and in whom noncalcified pulmonary nodules were evaluated according to volume and volume-doubling time, the chances of finding lung cancer 1 and 2 years after a negative first-round test were 1 in 1000 and 3 in 1000, respectively. (Current Controlled Trials number, ISRCTN63545820.)

Natural History of Patients with Subcentimeter Pulmonary Nodules Undergoing Hepatic Resection for Metastatic Colorectal Cancer

CT imaging frequently detects subcentimeter pulmonary nodules (SPN) in patients undergoing resection of colorectal cancer liver metastases. Their clinical significance is unknown. Patients were identified who underwent hepatic resection for colorectal cancer liver metastases between October 2004 and March 2006. The presence and imaging features of preoperative SPN were analyzed for their association with progression-free survival (PFS), disease-specific survival (DSS), and SPN progression. One hundred sixty patients underwent liver resection and 68 (43%) had SPN identified preoperatively. Median number of nodules was 1 (75(th) percentile: </=2 nodules) and median size of the largest was 3 mm (25(th) to 75(th) percentile: 2 to 5 mm). SPN were unilateral in 77%, calcified in 19%, solid in 92%, and smooth in contour in 95% of patients. At median follow-up of 31 months for survivors, SPN were proven to be metastatic disease in 35% of patients (24 of 68), either by radiographic increase in size or number (n = 12) or histologic confirmation after resection (n = 12). Median PFS for the 160 patients was 16 months and 3-year DSS was 78%. There was a trend toward shorter median PFS in patients with preoperative SPN compared with patients with no SPN (12 versus 20 months; p = 0.242). There was no difference in 3-year DSS (70% versus 83%; p = 0.46). SPN progression after hepatic resection did not substantially affect 3-year DSS. Calcified nodules were less likely to progress compared with noncalcified nodules (8% versus 42%; p = 0.03). SPN are common among patients undergoing resection of colorectal cancer liver metastases and approximately one-third of these will prove to be metastatic disease. Presence of limited preoperative SPN might be associated with shorter PFS after hepatectomy, but does not substantially impact 3-year DSS, and should not necessarily preclude resection of hepatic metastases.

Chest Wall Chondrosarcoma

A 75-year-old man presented with pleuritic chest pain and right shoulder pain. A palpable right anterior chest wall mass was noted on physical examination. His past medical history was significant for testicular cancer treated with radiation therapy in 1974. A computed tomography (CT) scan of the chest, performed without intravenous contrast due to renal insufficiency, revealed an 8-cm lobulated soft tissue mass arising from the right third anterior rib and involving the costal cartilage (Figure ​(Figure11). Scattered internal calcific deposits were present. It was uncertain if these represented chondroid matrix or destruction of calcified costal cartilage. The mass extended into the chest wall with elevation of the pectoralis muscles. Medially, the mass abutted the right anterior mediastinum. No additional osseous lesions or enlarged mediastinal or hilar nodes were seen. A few nonspecific 1- to 2-mm noncalcified pulmonary nodules were noted. CT of the abdomen and pelvis showed no evidence of metastatic disease. Figure 1 CT images through the chest at the level of the carina in both (a) soft tissue and (b) bone windows demonstrate a lytic mass involving the right anterior third rib, centered at the costochondral junction. A large, lobulated soft tissue component elevates ... Given the internal calcifications, the leading differential diagnostic consideration was chondrosarcoma; however, the classic “ring and arc” calcifications described in chondroid neoplasms were not definitively present on imaging. Metastasis was another consideration given the patient's history of testicular cancer; however, the location and appearance would be very atypical. The lesion appeared to arise from the chest wall and not the lung itself. Other considerations would include extramedullary plasmacytoma or lymphoma. An ultrasound-guided needle biopsy of the lesion, prepared for rapid cytologic evaluation using hematoxylin and eosin, showed a myxoid chondroid matrix with chondrocytes present (Figure ​(Figure22). The subsequently prepared paraffin block from the core biopsy showed a similar chondroid matrix with increasing cellularity at the periphery of the nodule (Figure ​(Figure33). Though no distinctly atypical chondrocytes were seen, the cellularity was concerning for a possible low-grade chondrosarcoma, and the tumor was excised along with the second, third, and fourth ribs. Grossly, the tumor did not involve the lateral margins but was 12 mm from the inferior resection margin of the fourth rib and 3 mm from the periosteal soft tissue of the superior aspect of the second rib. The neoplasm clearly demonstrated cartilage synthesis, as well as areas of hemorrhage and necrosis (50% of total tumor volume) (Figure ​(Figure44). Figure 2 Scrape preparation at time of ultrasound-guided biopsy demonstrating a myxoid chondroid matrix, increased cellularity, and chondrocytes. Diff-Quik stain, (a) ×100, (b) ×400. Figure 3 Paraffin cell block prepared from ultrasound-guided biopsy showing focal increased cellularity, chondroid matrix, and chondrocytes. Hematoxylin and eosin stain, (a) ×40, (b) ×100. Figure 4 Gross images of the resected tumor, showing the lesion (a) anteriorly, (b) posteriorly, (c) in cross-section, and (d) invading and destroying the third rib. Microscopically, the tumor showed features suggesting increasing histologic grade, such as areas with distinct marked hypercellularity, increasing nuclear size/atypia, and multinucleated cells (Figure ​(Figure55). However, the proliferation index, as demonstrated by MiB-1, was low, with most areas demonstrating 1% and focal areas demonstrating 5%. The tumor expanded the medullary cavity and in areas extended beyond the cortex, forming subpleural nodules posteriorly and involving the chest wall tissue anteriorly. The anterior chest wall surgical resection margin was focally involved by tumor. Extension through the pleural surface was not seen. Focal vascular invasion was present, with tumor grossly and microscopically surrounding and invading one blood vessel specifically. The tumor was considered grade 2. Figure 5 (a) Subpleural tumor nodule (×100). (b) Tumor at anterior resection margin (arrow) (×40). (c, d) Tumor expanding marrow cavity with markedly increased cellularity, nuclear atypia, and occasional multinucleated cells (×400). (e) ... Given the positive margin, radiation therapy was recommended. The patient received 3060 cGy of the planned 5940 cGy of radiation but could not complete the full course due to locoregional side effects. No additional therapy was recommended. A CT scan performed approximately 2 months after radiation therapy showed expected radiation changes and minimal pleural fluid without overt evidence of tumor recurrence. The patient is currently 4 months postradiation.

Giant cell arteritis on 18F‐FDG PET/CT

We present a case of incidentally noted giant cell arteritis in a patient undergoing 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT imaging. The patient was originally referred to PET/CT for staging of his renal transitional cell carcinoma. The patient was injected intravenously with 370 MBq of 18F-FDG. After a 60 min uptake period, PET/CT imaging was performed from the skull base to the mid thighs. A small para-aortic node in the region of the surgical bed showed increased tracer uptake of concern for malignancy. In addition, there were several non-calcified pulmonary nodules present, also concerning for malignancy. Incidentally noted was diffusely increased tracer uptake throughout the aorta and a thickened aortic wall on CT images. Diffuse tracer uptake was also present in the proximal branches of the aorta, including the carotid, iliac, femoral, and subclavian arteries. The patient had biopsy proven giant cell arteritis. Increased 18F-FDG uptake by the aorta on PET/CT imaging is an abnormal finding that prompts a more thorough assessment for malignancy, and also can indentify important co-morbidities in cancer patients. Evaluation of aortic uptake should be a routine practice in the interpretation of 18F-FDG PET/CT scans.

Molecular profile in body fluids in subjects enrolled in a randomised trial for lung cancer screening: Perspectives of integrated strategies for early diagnosis

The aim of this study was to evaluate the diagnostic value of a grid of molecular genetic markers detectable in sputum and plasma samples of individuals enrolled in a lung cancer screening program with low-dose CT. Subjects enrolled in the baseline screening round of the ITALUNG (randomised) screening trial were invited to provide biological specimens for molecular analysis (1356 subjects out of 1406). We included 98 subjects in this analysis. There was a highly statistically significant difference between proportion of subjects with a negative baseline CT screening test who were positive to allelic imbalance, and those with a non-calcified nodule (NCN greater than or equal to 5 mm), the reason of recall for all suspects at CT Scan ( χ 2: 22.9; P < 0.0001). Allelic imbalance showed good performance for screening of NCN ≥5 mm. In subjects recalled for NCN ≥5 mm, LOH, K-ras mutations and high levels of free plasma DNA (>5 ng/ml plasma) might be important to support clinical decision making for further follow-up and repeated screening. This study, embedded in an early diagnosis randomised trial, suggests that a multi-screening approach integrating imaging technique and a biomolecular marker panel is worth of further investigation.

A novel multithreshold method for nodule detection in lung CT

Multislice computed tomography (MSCT) is a valuable tool for lung cancer detection, thanks to its ability to identify noncalcified nodules of small size (from about 3 mm). Due to the large number of images generated by MSCT, there is much interest in developing computer-aided detection (CAD) systems that could assist radiologists in the lung nodule detection task. A complete multistage CAD system, including lung boundary segmentation, regions of interest (ROIs) selection, feature extraction, and false positive reduction is presented. The selection of ROIs is based on a multithreshold surface-triangulation approach. Surface triangulation is performed at different threshold values, varying from a minimum to a maximum value in a wide range. At a given threshold value, a ROI is defined as the volume inside a connected component of the triangulated isosurface. The evolution of a ROI as a function of the threshold can be represented by a treelike structure. A multithreshold ROI is defined as a path on this tree, which starts from a terminal ROI and ends on the root ROI. For each ROI, the volume, surface area, roundness, density, and moments of inertia are computed as functions of the threshold and used as input to a classification system based on artificial neural networks. The method is suitable to detect different types of nodules, including juxta-pleural nodules and nodules connected to blood vessels. A training set of 109 low-dose MSCT scans made available by the Pisa center of the Italung-CT trial and annotated by expert radiologists was used for the algorithm design and optimization. The system performance was tested on an independent set of 23 low-dose MSCT scans coming from the Pisa Italung-CT center and on 83 scans made available by the Lung Image Database Consortium (LIDC) annotated by four expert radiologists. On the Italung-CT test set, for nodules having a diameter greater than or equal to 3 mm, the system achieved 84% and 71% sensitivity at false positive/scan rates of 10 and 4, respectively. For nodules having a diameter greater than or equal to 4 mm, the sensitivities were 97% and 80% at false positive/scan rates of 10 and 4, respectively. On the LIDC data set, the system achieved a 79% sensitivity at a false positive/scan rate of 4 in the detection of nodules with a diameter greater than or equal to 3 mm that have been annotated by all four radiologists.

Cumulative risk for a false-positive test using low-dose computed tomography in lung cancer screening

CRA1502 Background: Screening with low-dose computed tomography (LDCT) has been promoted as the best hope for curing lung cancer. However, cumulative false-positive (FP) rates have never been formally reported. We quantified the cumulative risk of receiving ≥1 FP test for individuals in a lung cancer screening program with 2 annual screens. Methods: Prior to the ongoing National Lung Screening Trial (NLST), a definitive randomized controlled trial of LDCT versus single-view chest xray (CXR), a randomized controlled feasibility trial was conducted at six NLST centers. Participants (55–74 years at entry, current or former smokers, and ≥ 30 pack/year smoking history) were offered a baseline LDCT (N = 1,610) or CXR (N = 1,580), and one repeat annual screen, and were followed for 1 year after their final screen. Participants who received at least one screening exam were eligible for this analysis. Exclusion criteria included chest CT in the past 24 months or history of lung cancer. A positive screen was any noncalcified nodule ≥ 4mm or other radiographic finding deemed suspicious for cancer. A FP was a positive screen with: 1) a completed negative work-up, or 2) ≥ 12 months follow-up with no cancer diagnosis. Results: Using a Kaplan-Meier analysis, an individual's cumulative probability of ≥ 1 FP LDCT was 21% (95% CI, 19%–23%) after one screen and 33% (95% CI, 30%–35%) after two. The cumulative probability of ≥ 1 FP CXR was 9% (95% CI, 8%–11%) and 15% (95% CI, 13%–16%) after one and two screens, respectively. On multivariable analysis, higher odds of FP for LDCT were associated with increased participant age (&gt;64 years) (OR 1.34, 95% CI, 1.04–1.73); current versus former smoker status trended toward higher FP odds (OR 1.22, 95% CI, 0.95–1.56). 6.6% of participants with a FP LDCT underwent an invasive diagnostic follow-up procedure; 1.6% had major surgery. 4.2% of participants with a FP CXR underwent an invasive diagnostic follow-up procedure; 1.9% had major surgery. Conclusions: Risks of LDCT FP are substantial after only two annual examinations; the potential resulting economic, psychosocial, and physical burdens of this modality warrant investigation. No significant financial relationships to disclose.

Cumulative risk for a false-positive test using low-dose computed tomography in lung cancer screening

CRA1502 Background: Screening with low-dose computed tomography (LDCT) has been promoted as the best hope for curing lung cancer. However, cumulative false-positive (FP) rates have never been formally reported. We quantified the cumulative risk of receiving ≥1 FP test for individuals in a lung cancer screening program with 2 annual screens. Methods: Prior to the ongoing National Lung Screening Trial (NLST), a definitive randomized controlled trial of LDCT versus single-view chest xray (CXR), a randomized controlled feasibility trial was conducted at six NLST centers. Participants (55–74 years at entry, current or former smokers, and ≥ 30 pack/year smoking history) were offered a baseline LDCT (N = 1,610) or CXR (N = 1,580), and one repeat annual screen, and were followed for 1 year after their final screen. Participants who received at least one screening exam were eligible for this analysis. Exclusion criteria included chest CT in the past 24 months or history of lung cancer. A positive screen was any noncalcified nodule ≥ 4mm or other radiographic finding deemed suspicious for cancer. A FP was a positive screen with: 1) a completed negative work-up, or 2) ≥ 12 months follow-up with no cancer diagnosis. Results: Using a Kaplan-Meier analysis, an individual's cumulative probability of ≥ 1 FP LDCT was 21% (95% CI, 19%–23%) after one screen and 33% (95% CI, 30%–35%) after two. The cumulative probability of ≥ 1 FP CXR was 9% (95% CI, 8%–11%) and 15% (95% CI, 13%–16%) after one and two screens, respectively. On multivariable analysis, higher odds of FP for LDCT were associated with increased participant age (>64 years) (OR 1.34, 95% CI, 1.04–1.73); current versus former smoker status trended toward higher FP odds (OR 1.22, 95% CI, 0.95–1.56). 6.6% of participants with a FP LDCT underwent an invasive diagnostic follow-up procedure; 1.6% had major surgery. 4.2% of participants with a FP CXR underwent an invasive diagnostic follow-up procedure; 1.9% had major surgery. Conclusions: Risks of LDCT FP are substantial after only two annual examinations; the potential resulting economic, psychosocial, and physical burdens of this modality warrant investigation. No significant financial relationships to disclose.

Significance of Cardiac Computed Tomography Incidental Findings in Acute Chest Pain

Background Coronary computed tomography angiography might improve the management of patients presenting to the emergency department with acute chest pain; however, noncoronary incidental findings are frequently detected. The prevalence and clinical significance of these findings have not been well described. Methods Consecutive patients presenting to the emergency department with acute chest pain and inconclusive initial evaluation between May 2005 and May 2007 underwent 64-slice coronary computed tomography angiography before hospital admission with noncoronary incidental findings immediately reported. An expert panel adjudicated which incidental findings changed in-hospital patient management, and projections for additional testing were based on standard medical practice. Results Among 395 patients (37.0% were female, mean age 53 ± 12 years), incidental findings were detected in 44.8% (n = 177): noncalcified pulmonary nodules (n = 94, 23.8%), simple liver cysts (n = 26, 6.6%), calcified pulmonary nodules (n = 16, 4.1%), and contrast-enhancing liver lesions (n = 9, 2.3%). In-hospital management was changed because of incidental finding reporting in 5 patients (1.3%), and a potential alternative diagnosis was offered in another 16 patients (4.1%). Subsequent diagnostic imaging tests were recommended in 81 patients (20.5%), including 74 chest computed tomography scans. After 6 months, biopsy was performed in 3 patients, revealing cancer in 2 (0.5%) who underwent successful tumor resection. Conclusion Clinically important findings are detected in up to 5% of patients with a lead symptom of acute chest pain and low to intermediate likelihood of acute coronary syndrome, but only few directly change patient management; 21% are recommended for further imaging tests, resulting in invasive procedures and detection of cancer in few patients.

Incidental lung nodules on CT examinations of the abdomen: Prevalence and reporting rates in the PACS era

Objectives To retrospectively evaluate prevalence, reporting rates and clinical implications of incidental pulmonary nodules detected in multidetector computed tomography (MDCT) abdominal studies. Materials and methods Abdominal MDCT studies of 243 consecutive patients, 94 of whom had a history of cancer, were evaluated. Lung bases included in the scan were reviewed on a PACS workstation with different window settings and post-processing techniques. Nodules were classified according to their density (calcified, solid noncalcified, non-solid, part-solid) and size (<4 mm; 4–6 mm; 6–8 mm; >8 mm). The study findings were compared with the corresponding radiologic reports. Previous of following CT studies, when available from the PACS, were also reviewed to evaluate changes in number and size of the detected nodules. Results An average of 8.2 cm of lung parenchyma was imaged in each patient. 213 noncalcified nodules (NCNs) were identified in 95 patients (39.1%) but only 8 patients (8.4%) had it mentioned in the final report. Comparison CT studies were available for 44 out of the 95 positive patients showing disappearance of the nodules in 2 cases, no interval change in 26 and progression in size and/or number in 16 patients, in whom a final diagnosis of metastasis or primary lung cancers was achieved. Conclusion Radiologists tend to overlook lung portions on abdominal CT studies. Underreporting may affect patient care and have medico-legal implications since images are permanently stored in digital format on PACS and CD-ROMs. Management of the discovered nodules should be tailored to the clinical situation of the patient, and particular care should be reserved to patients with oncologic history.

Lung cancer screening using low-dose computed tomography in at-risk individuals: The Toronto experience

ObjectiveThe Department of Medical Imaging at the University Health Network in Toronto is performing a lung cancer screening study, utilizing low-dose computed tomography (LDCT) as the modality. Baseline and annual repeat results are reported on the first 3352 participants, enrolled between June 2003 and May 2007. MethodsEnrollment was limited to those aged 50 years or older, with a smoking history of at least 10 pack-years, no previous cancer and general good health. A helical low-dose CT (LDCT) of the chest was performed using 120kVp, 40–60mA, images were reconstructed with 1–1.25mm overlapping slices. The primary objectives were the detection of parenchymal nodules and diagnosis of early stage lung cancer. Baseline LDCTs were termed positive if at least one indeterminate non-calcified nodule 5mm or larger in size, or non-solid nodule 8mm or larger in size was identified. Follow up periods for individuals with a positive baseline LDCT were determined by nodule characteristics. ResultsThe median age at baseline was 60 years (range 50–83), with a median of 30 pack-years of cigarette smoking (range 10–189). Baseline CT evaluations were positive in 600 (18%) participants. To date, 2686 (80%) of the participants have returned for at least one annual repeat screening LDCT. Biopsies have been recommended for 82 participants since the study began, and 64 have been diagnosed with screen-detected cancer (62 lung, two plasmacytoma of the rib). A total of 65 lung cancers have been diagnosed (62 screen-detected, 3 interim), 57 are NSCLC (82% with known stage are stage I or II) and the rate of surgical resection was 80%. Sensitivity and specificity of the protocol in successfully diagnosing early stage lung cancers were 87.7% and 99.3%, respectively. ConclusionsData indicate that LDCT can identify small lung cancers in an at-risk population. The diagnostic algorithm results in few false-positive invasive procedures. Most cancers are detected at an early stage, where the cancer is resectable with a greater potential for cure. Long-term follow up of lung cancer cases will be carried out to determine survival.