Diagnosis and Treatment of Pulmonary Sarcoidosis: A Review.

Importance: Sarcoidosis is an inflammatory granulomatous disease of unknown cause that affects an estimated 2 to 160 people per 100 000 worldwide and can involve virtually any organ. Approximately 10% to 30% of patients with sarcoidosis develop progressive pulmonary disease. Observation: Among patients with pulmonary sarcoidosis, the rate of spontaneous remission without serious sequelae ranges from 10% to 82%. However, lung disease progression occurs in more than 10% of patients and can result in fibrocystic architectural distortion of the lung, which is associated with a mortality rate of 12% to 18% within 5 years. Overall, the mortality rate for sarcoidosis is approximately 7% within a 5-year follow-up period. Worldwide, more than 60% of deaths from sarcoidosis are due to pulmonary involvement; however, more than 70% of deaths from sarcoidosis are due to cardiac involvement in Japan. Up to 70% of patients with advanced pulmonary sarcoidosis develop precapillary pulmonary hypertension, which is associated with a 5-year mortality rate of approximately 40%. Patients with sarcoidosis and precapillary pulmonary hypertension should be treated with therapies such as phosphodiesterase inhibitors and prostacyclin analogues. Although optimal doses of oral glucocorticoids for pulmonary sarcoidosis are unknown, oral prednisone typically starting at a dose of 20 mg/d to 40 mg/d for 2 to 6 weeks is recommended for patients who are symptomatic (cough, dyspnea, and chest pain) and have parenchymal infiltrates and abnormal pulmonary function test results. Oral glucocorticoids can be tapered over 6 to 18 months if symptoms, pulmonary function test results, and radiographs improve. Prolonged use of oral glucocorticoids may be required to control symptoms and stabilize disease. Patients without adequate improvement while receiving a dose of prednisone of 10 mg/d or greater or those with adverse effects due to glucocorticoids may be prescribed immunosuppressive agents, such as methotrexate, azathioprine, or an anti-tumor necrosis factor medication, either alone or with glucocorticoids combined with appropriate microbial prophylaxis for Pneumocystis jiroveci and herpes zoster. Effective treatments are not available for advanced fibrocystic pulmonary disease. Conclusions and Relevance: Sarcoidosis has a mortality rate of approximately 7% within a 5-year follow-up period. More than 10% of patients with pulmonary sarcoidosis develop progressive disease and more than 60% of deaths are due to advanced pulmonary sarcoidosis. Oral glucocorticoids with or without another immunosuppressive agent are the first-line therapy for symptomatic patients with abnormal pulmonary function test results and lung infiltrates. Patients with sarcoidosis and precapillary pulmonary hypertension should be treated with therapies such as phosphodiesterase inhibitors and prostacyclin analogues.

Detection and Early Referral of Patients With Interstitial Lung Abnormalities: An Expert Survey Initiative.

BACKGROUND: Interstitial lung abnormalities (ILA) may represent undiagnosed early-stage or subclinical interstitial lung disease (ILD). ILA are often observed incidentally in patients who subsequently develop clinically overt ILD. There is limited information on consensus definitions for, and the appropriate evaluation of, ILA. Early recognition of patients with ILD remains challenging, yet critically important. Expert consensus could inform early recognition and referral. RESEARCH QUESTION: Can consensus-based expert recommendations be identified to guide clinicians in the recognition, referral, and follow-up of patients with or at risk of developing early ILDs? STUDY DESIGN AND METHODS: Pulmonologists and radiologists with expertise in ILD participated in two iterative rounds of surveys. The surveys aimed to establish consensus regarding ILA reporting, identification of patients with ILA, and identification of populations that might benefit from screening for ILD. Recommended referral criteria and follow-up processes were also addressed. Threshold for consensus was defined a priori as ≥ 75% agreement or disagreement. RESULTS: Fifty-five experts were invited and 44 participated; consensus was reached on 39 of 85 questions. The following clinically important statements achieved consensus: honeycombing and traction bronchiectasis or bronchiolectasis indicate potentially progressive ILD; honeycombing detected during lung cancer screening should be reported as potentially significant (eg, with the Lung CT Screening Reporting and Data System "S-modifier" [Lung-RADS; which indicates clinically significant or potentially significant noncancer findings]), recommending referral to a pulmonologist in the radiology report; high-resolution CT imaging and full pulmonary function tests should be ordered if nondependent subpleural reticulation, traction bronchiectasis, honeycombing, centrilobular ground-glass nodules, or patchy ground-glass opacity are observed on CT imaging; patients with honeycombing or traction bronchiectasis should be referred to a pulmonologist irrespective of diffusion capacity values; and patients with systemic sclerosis should be screened with pulmonary function tests for early-stage ILD. INTERPRETATION: Guidance was established for identifying clinically relevant ILA, subsequent referral, and follow-up. These results lay the foundation for developing practical guidance on managing patients with ILA.

Radiographic and Histopathologic Features in Sarcoidosis: A Pictorial Display.

Sarcoidosis is a multisystemic granulomatous disorder that can affect virtually any organ. However, pulmonary and thoracic lymph node involvement predominates; abnormalities on chest radiographs are present in 80 to 90% of patients with sarcoidosis. High-resolution computed tomographic (HRCT) scans are superior to chest X-rays in assessing extent of disease, and some CT features may discriminate an active inflammatory component (which may be amenable to therapy) from fibrosis (for which therapy is not indicated). Typical findings on HRCT include micronodules, perilymphatic and bronchocentric distribution, perihilar opacities, and varying degrees of fibrosis. Less common findings on CT include mass-like or alveolar opacities, miliary opacities, mosaic attenuation, honeycomb cysts, and cavitation. With progressive disease, fibrosis, architectural distortion, upper lobe volume loss with hilar retraction, coarse linear bands, cysts, and bullae may be observed. We discuss the salient CT findings in patients with sarcoidosis (with a major focus on pulmonary features) and present classical radiographic and histopathological images of a few extrapulmonary sites.

Multicenter Study of Metastatic Lung Tumors Targeted by Interventional Cryoablation Evaluation (SOLSTICE).

OBJECTIVE: To assess the safety and local recurrence-free survival in patients after cryoablation for treatment of pulmonary metastases. METHODS: This multicenter, prospective, single-arm, phase 2 study included 128 patients with 224 lung metastases treated with percutaneous cryoablation, with 12 and 24 months of follow-up. The patients were enrolled on the basis of the outlined key inclusion criteria, which include one to six metastases from extrapulmonary cancers with a maximal diameter of 3.5 cm. Time to progression of the index tumor(s), metastatic disease, and overall survival rates were estimated using the Kaplan-Meier method. Complications were captured for 30 days after the procedure, and changes in performance status and quality of life were also evaluated. RESULTS: Median size of metastases was 1.0 plus or minus 0.6 cm (0.2-4.5) with a median number of tumors of 1.0 plus or minus 1.2 cm (one to six). Local recurrence-free response (local tumor efficacy) of the treated tumor was 172 of 202 (85.1%) at 12 months and 139 of 180 (77.2%) at 24 months after the initial treatment. After a second cryoablation treatment for recurrent tumor, secondary local recurrence-free response (local tumor efficacy) was 184 of 202 (91.1%) at 12 months and 152 of 180 (84.4%) at 24 months. Kaplan-Meier estimates of 12- and 24-month overall survival rates were 97.6% (95% confidence interval: 92.6-99.2) and 86.6% (95% confidence interval: 78.7-91.7), respectively. Rate of pneumothorax that required pleural catheter placement was 26% (44/169). There were eight grade 3 complication events in 169 procedures (4.7%) and one (0.6%) grade 4 event. CONCLUSION: Percutaneous cryoablation is a safe and effective treatment for pulmonary metastases.

Genomic Adequacy from Solid Tumor Core Needle Biopsies of ex Vivo Tissue and in Vivo Lung Masses: Prospective Study.

Purpose To identify the variables and factors that affect the quantity and quality of nucleic acid yields from imaging-guided core needle biopsy. Materials and Methods This study was approved by the institutional review board and compliant with HIPAA. The authors prospectively obtained 232 biopsy specimens from 74 patients (177 ex vivo biopsy samples from surgically resected masses were obtained from 49 patients and 55 in vivo lung biopsy samples from computed tomographic [CT]-guided lung biopsies were obtained from 25 patients) and quantitatively measured DNA and RNA yields with respect to needle gauge, number of needle passes, and percentage of the needle core. RNA quality was also assessed. Significance of correlations among variables was assessed with analysis of variance followed by linear regression. Conditional probabilities were calculated for projected sample yields. Results The total nucleic acid yield increased with an increase in the number of needle passes or a decrease in needle gauge (two-way analysis of variance, P < .0001 for both). However, contrary to calculated differences in volume yields, the effect of needle gauge was markedly greater than the number of passes. For example, the use of an 18-gauge versus a 20-gauge biopsy needle resulted in a 4.8-5.7 times greater yield, whereas a double versus a single pass resulted in a 2.4-2.8 times greater yield for 18- versus 20-gauge needles, respectively. Ninety-eight of 184 samples (53%) had an RNA integrity number of at least 7 (out of a possible score of 10). Conclusion With regard to optimizing nucleic acid yields in CT-guided lung core needle biopsies used for genomic analysis, there should be a preference for using lower gauge needles over higher gauge needles with more passes. ©RSNA, 2016 Online supplemental material is available for this article. An earlier incorrect version of this article appeared online. This article was corrected on October 21, 2016.

Defining New Metrics in Microwave Ablation of Pulmonary Tumors: Ablation Work and Ablation Resistance Score.

PURPOSE: To investigate pulmonary microwave ablation metrics including ablation work, ablation resistance score, and involution. MATERIALS AND METHODS: Retrospective review was performed of 98 pulmonary tumor ablations using the NeuWave Certus Microwave Ablation System (NeuWave Medical, Madison, Wisconsin) in 71 patients (32 men and 39 women; mean age, 64.7 y ± 11.5). Ablation work was defined as sum of (power) * (time) * (number of antennas) for all phases during an ablation procedure. Ablation zone was measured on CT at 3 time points: after procedure, 1-3 months (mean 47 d), and 3-12 months (mean 292 d). Ablation zones were scored based on location for pulmonary lobe (upper = 1, middle/lingula = 2, lower = 3) and region (peripheral = 1, parenchymal = 2, central = 3), and the 2 were summed for ablation resistance score. RESULTS: Ablation zone on CT at 1-3 months was significantly smaller in regions with higher ablation resistance score (P < .05). There was a significant correlation between ablation work and ablation zone measured on CT performed after procedure (P < .001), at 1-3 months (P < .001), and at 3-12 months (P < .05). Ablation zone significantly decreased from after procedure to 1-3 months (P < .001) and from 1-3 months to 3-12 months (P < .001), with change from after procedure to 1-3 months significantly greater (P < .01). CONCLUSIONS: Pulmonary microwave ablation zone is significantly smaller in regions with higher ablation resistance score. Ablation work correlates to ablation zone with a nonlinear involution pattern in the first year and may be useful for planning before the procedure.

Radiofrequency ablation of lung tumors: imaging features of the postablation zone.

Radiofrequency ablation (RFA) is used to treat pulmonary malignancies. Although preliminary results are suggestive of a survival benefit, local progression rates are appreciable. Because a patient can undergo repeat treatment if recurrence is detected early, reliable post-RFA imaging follow-up is critical. The purpose of this article is to describe (a) an algorithm for post-RFA imaging surveillance; (b) the computed tomographic (CT) appearance, size, enhancement, and positron emission tomographic (PET) metabolic activity of the ablation zone; and (c) CT, PET, and dual-modality imaging with PET and CT (PET/CT) features suggestive of partial ablation or tumor recurrence and progression. CT is routinely used for post-RFA follow-up. PET and PET/CT have emerged as auxiliary follow-up techniques. CT with nodule densitometry may be used to supplement standard CT. Post-RFA follow-up was divided into three phases: early (immediately after to 1 week after RFA), intermediate (>1 week to 2 months), and late (>2 months). CT and PET imaging features suggestive of residual or recurrent disease include (a) increasing contrast material uptake in the ablation zone (>180 seconds on dynamic images), nodular enhancement measuring more than 10 mm, any central enhancement greater than 15 HU, and enhancement greater than baseline anytime after ablation; (b) growth of the RFA zone after 3 months (compared with baseline) and definitely after 6 months, peripheral nodular growth and change from ground-glass opacity to solid opacity, regional or distant lymph node enlargement, and new intrathoracic or extrathoracic disease; and (c) increased metabolic activity beyond 2 months, residual activity centrally or at the ablated tumor, and development of nodular activity.

Emphysema lung lobe volume reduction: effects on the ipsilateral and contralateral lobes.

OBJECTIVES: To investigate volumetric and density changes in the ipsilateral and contralateral lobes following volume reduction of an emphysematous target lobe. METHODS: The study included 289 subjects with heterogeneous emphysema, who underwent bronchoscopic volume reduction of the most diseased lobe with endobronchial valves and 132 untreated controls. Lobar volume and low-attenuation relative area (RA) changes post-procedure were measured from computed tomography images. Regression analysis (Spearman's rho) was performed to test the association between change in the target lobe volume and changes in volume and density variables in the other lobes. RESULTS: The target lobe volume at full inspiration in the treatment group had a mean reduction of -0.45 L (SE = 0.034, P < 0.0001), and was associated with volume increases in the ipsilateral lobe (rho = -0.68, P < 0.0001) and contralateral lung (rho = -0.16, P = 0.006), and overall reductions in expiratory RA (rho = 0.31, P < 0.0001) and residual volume (RV)/total lung capacity (TLC) (rho = 0.13, P = 0.03). CONCLUSIONS: When the volume of an emphysematous target lobe is reduced, the volume is redistributed primarily to the ipsilateral lobe, with an overall reduction. Image-based changes in lobar volumes and densities indicate that target lobe volume reduction is associated with statistically significant overall reductions in air trapping, consistent with expansion of the healthier lung. KEY POINTS: Computed tomography allows assessment of the treatment of emphysema with endobronchial valves. • Endobronchial valves can reduce the volume of an emphysematous lung lobe. • Compensatory expansion is greater in ipsilateral lobes than in the contralateral lung. • Reduced air trapping is measurable by RV/TLC and smaller low attenuation area.

Radiofrequency ablation of subpleural lung malignancy: reduced pain using an artificially created pneumothorax.

One of the main issues with radiofrequency (RF) ablation of the subpleural lung malignancy is pain management during and after RF ablation. In this article, we present a case that utilized a technique to decrease the pain associated with RF ablation of a malignancy located within the subpleural lung. Under CT guidance, we created an artificial pneumothorax prior to the RF ablation, which resulted in minimizing the pain usually experienced during and after the procedure. It also decreased the amount of pain medications usually used in patients undergoing RF ablation of a subpleural lung lesion.

The effect of lung volume on nodule size on CT.

RATIONALE AND OBJECTIVES: We sought to determine how measures of nodule diameter and volume on computed tomography (CT) vary with changes in inspiratory level. MATERIALS AND METHODS: CT scans were performed with inspiration suspended at total lung capacity (TLC) and then at residual volume (RV) in 41 subjects, in whom 75 indeterminate lung nodules were detected. A fully automated contouring program was used to segment the lungs; followed by segmentation of all nodules and the corresponding lobe using semiautomated contouring in both TLC and RV scans. The percent changes in lung and lobar volumes between TLC and RV were correlated with percent changes in nodule diameters and volumes. RESULTS: Both nodule diameter and volume varied nonuniformly from TLC to RV-some nodules decreased in size, while others increased. There was a 16.8% mean change in absolute volume across all nodules. Stratified by size, the mean value of the absolute percent volume changes for nodules > or =5 mm and <5 mm were not significantly different (P = .26). Stratified by maximum attenuation, the mean value of the absolute percent volume changes between the TLC and RV series for noncalcified (17.7%, SD = 13.1) and completely calcified nodules (8.6% SD = 5.7) were significantly different (P < .05). CONCLUSION: Significant differences in nodule size were measured between TLC and RV scans. This has important implications for standardizing acquisition protocols in any setting where size and, more important, size change are being used for purposes of lung cancer staging, nodule characterization, or treatment response assessment.