Pulmonary nodules are identified in approximately 1.6 million patients per year in the US and are detected on approximately 30% of computed tomographic (CT) images of the chest. Optimal treatment of an individual with a pulmonary nodule can lead to early detection of cancer while minimizing testing for a benign nodule.At least 95% of all pulmonary nodules identified are benign, most often granulomas or intrapulmonary lymph nodes. Smaller nodules are more likely to be benign. Pulmonary nodules are categorized as small solid (<8 mm), larger solid (≥8 mm), and subsolid. Subsolid nodules are divided into ground-glass nodules (no solid component) and part-solid (both ground-glass and solid components). The probability of malignancy is less than 1% for all nodules smaller than 6 mm and 1% to 2% for nodules 6 mm to 8 mm. Nodules that are 6 mm to 8 mm can be followed with a repeat chest CT in 6 to 12 months, depending on the presence of patient risk factors and imaging characteristics associated with lung malignancy, clinical judgment about the probability of malignancy, and patient preferences. The treatment of an individual with a solid pulmonary nodule 8 mm or larger is based on the estimated probability of malignancy; the presence of patient comorbidities, such as chronic obstructive pulmonary disease and coronary artery disease; and patient preferences. Management options include surveillance imaging, defined as monitoring for nodule growth with chest CT imaging, positron emission tomography-CT imaging, nonsurgical biopsy with bronchoscopy or transthoracic needle biopsy, and surgical resection. Part-solid pulmonary nodules are managed according to the size of the solid component. Larger solid components are associated with a higher risk of malignancy. Ground-glass pulmonary nodules have a probability of malignancy of 10% to 50% when they persist beyond 3 months and are larger than 10 mm in diameter. A malignant nodule that is entirely ground glass in appearance is typically slow growing. Current bronchoscopy and transthoracic needle biopsy methods yield a sensitivity of 70% to 90% for a diagnosis of lung cancer.Pulmonary nodules are identified in approximately 1.6 million people per year in the US and approximately 30% of chest CT images. The treatment of an individual with a pulmonary nodule should be guided by the probability that the nodule is malignant, safety of testing, the likelihood that additional testing will be informative, and patient preferences.

Lung cancer is a common disease and the leading cause of cancer-related mortality, with non-small cell lung cancer (NSCLC) accounting for the majority of cases. Following diagnosis of lung cancer, accurate staging is essential to guide clinical management and inform prognosis. Positron emission tomography (PET) in conjunction with computed tomography (CT)-as PET-CT has developed as an important tool in the multi-disciplinary management of lung cancer. This article will review the current evidence for the role of F-18-fluorodeoxyglucose (FDG) PET-CT in NSCLC diagnosis, staging, response assessment and follow up.

(18)F-FDG PET/CT has been used to differentiate malignant solid lung nodules from benign nodules. We assess the feasibility of integrated (18)F-FDG PET/CT for the differentiation of malignancy from inflammation manifested as ground-glass nodules (GGNs) on chest CT.A total of 68 GGNs in 45 patients (M:F=24:21; mean age, 61) fulfilled the following criteria: (a) nodules composed of >/=50% ground-glass opacity, (b) patients who underwent integrated PET/CT within 1 week following dedicated chest CT, (c) definitive diagnosis determined by pathological specimen or at least 9 months of follow-up, and (d) lesions >/=10mm in diameter. 36 malignant GGNs were pathologically proved as adenocarcinoma (n=20), bronchioloalveolar carcinoma (n=11), low-grade lymphoma (n=3), metastatic mucinous adenocarcinoma (n=1) and unknown low-grade malignancy (n=1). 32 inflammatory GGNs were confirmed as pneumonic infiltration as they had disappeared on follow-up CT and were associated with compatible clinical features (n=26) or as chronic inflammation with fibrosis by VATS biopsy (n=6). Using CT density histogram analysis, 14 were classified as pure GGNs and 54 as part-solid nodules. Integrated PET/CT was evaluated by measuring the maximum standardized uptake value (SUV) at the region of interest located at each lesion. The Mann-Whitney U test was performed to compare the SUV of malignancy and inflammation. The optimal cut-off value of SUV to differentiate malignancy from inflammation was determined using a receiver operating characteristic-based positive test. Sensitivity, specificity, accuracy, and positive predictive values (PPV) and negative predictive values (NPV) were calculated at the level of the optimal cut-off value. SUV showing 100% PPV for inflammatory GGNs was evaluated.In part-solid nodules, the maximum SUV was significantly higher in inflammation (2.00+/-1.18; range, 0.48-5.60) than in malignancy (1.26+/-0.71; range, 0.32-2.6) (P=0.018). On the other hand, in pure GGNs, the maximum SUV of malignancy (0.64+/-0.19; range, 0.43-0.96) and inflammation (0.74+/-0.28; range, 0.32-1.00) showed no difference (P=0.37). Using the optimal cut-off value of SUV as 1.2 (P=0.01) sensitivity, specificity, accuracy, PPV and NPV in part-solid nodules were 62.1%, 80.0%, 70.4%, 78.3% and 64.5%, respectively. Six part-solid nodules, which showed a maximum SUV of higher than 2.6, were all inflammations.The part-solid nodules with positive FDG-PET could be inflammatory nodules rather than malignant nodules. This is a quite paradoxical result when considering the basic knowledge that malignant pulmonary nodules have higher glucose metabolism.

Focal bronchioloalveolar cell carcinoma (BAC) has been reported as often being negative on 2-[fluorine-18] fluoro-2-deoxy-D-glucose (FDG-PET) scans, but no studies have examined the FDG-PET findings of both the focal and multifocal forms of the disease. The purpose of this study was to examine the sensitivity of PET in detecting both forms of BAC.A retrospective review of our tumor registry revealed 15 patients who had pathologically proved BAC and who had undergone FDG-PET imaging. FDG-PET scans were interpreted as positive if the tumor demonstrated activity that was greater than the mediastinal blood pool.Eight patients had focal BAC, and seven patients had multifocal disease. Nine of the 15 patients (60%) had a positive PET scan, and of these, six (67%) had multifocal disease. Six of the 15 patients (40%) had negative PET scans, and of these, five patients (83%) had the solitary form of disease. The sensitivity for focal tumors was 38%, and the sensitivity for the multifocal form was 86%.Our data confirm previous reports describing a high percentage of false negative PET scans in the setting of focal BAC. However, in the presence of multifocal disease, FDG-PET seems to be highly sensitive.

The detection of pulmonary nodules (PNs) is likely to increase, especially with the release of the National Lung Screen Trials. When tissue diagnosis is desired, transthoracic needle aspiration (TTNA) is recommended. Several guided-bronchoscopy technologies have been developed to improve the yield of transbronchial biopsy for PN diagnosis: electromagnetic navigation bronchoscopy (ENB), virtual bronchoscopy (VB), radial endobronchial ultrasound (R-EBUS), ultrathin bronchoscope, and guide sheath. We undertook this meta-analysis to determine the overall diagnostic yield of guided bronchoscopy using one or a combination of the modalities described here.We performed a MEDLINE search using “bronchoscopy” and “solitary pulmonary nodule.” Studies evaluating the diagnostic yield of ENB, VB, R-EBUS, ultrathin bronchoscope, and/or guide sheath for peripheral nodules were included. The overall diagnostic yield and yield based on size were extracted. Adverse events, if reported, were recorded. Meta-analysis techniques incorporating inverse variance weighting and a random-effects meta-analysis approach were used.A total of 3,052 lesions from 39 studies were included. The pooled diagnostic yield was 70%, which is higher than the yield for traditional transbronchial biopsy. The yield increased as the lesion size increased. The pneumothorax rate was 1.5%, which is significantly smaller than that reported for TTNA.This meta-analysis shows that the diagnostic yield of guided bronchoscopic techniques is better than that of traditional transbronchial biopsy. Although the yield remains lower than that of TTNA, the procedural risk is lower. Guided bronchoscopy may be an alternative or be complementary to TTNA for tissue sampling of PN, but further study is needed to determine its role in the evaluation of peripheral pulmonary lesions.

Electromagnetic navigation bronchoscopy (ENB) is a minimally invasive technology that guides endoscopic tools to pulmonary lesions. ENB has been evaluated primarily in small, single-center studies; thus, the diagnostic yield in a generalizable setting is unknown.NAVIGATE is a prospective, multicenter, cohort study that evaluated ENB using the superDimension navigation system (Medtronic, Minneapolis, Minnesota). In this United States cohort analysis, 1215 consecutive subjects were enrolled at 29 academic and community sites from April 2015 to August 2016.The median lesion size was 20.0 mm. Fluoroscopy was used in 91% of cases (lesions visible in 60%) and radial endobronchial ultrasound in 57%. The median ENB planning time was 5 minutes; the ENB-specific procedure time was 25 minutes. Among 1157 subjects undergoing ENB-guided biopsy, 94% (1092 of 1157) had navigation completed and tissue obtained. Follow-up was completed in 99% of subjects at 1 month and 80% at 12 months. The 12-month diagnostic yield was 73%. Pathology results of the ENB-aided tissue samples showed malignancy in 44% (484 of 1092). Sensitivity, specificity, positive predictive value, and negative predictive value for malignancy were 69%, 100%, 100%, and 56%, respectively. ENB-related Common Terminology Criteria for Adverse Events grade 2 or higher pneumothoraces (requiring admission or chest tube placement) occurred in 2.9%. The ENB-related Common Terminology Criteria for Adverse Events grade 2 or higher bronchopulmonary hemorrhage and grade 4 or higher respiratory failure rates were 1.5% and 0.7%, respectively.NAVIGATE shows that an ENB-aided diagnosis can be obtained in approximately three-quarters of evaluable patients across a generalizable cohort based on prospective 12-month follow-up in a pragmatic setting with a low procedural complication rate.Copyright © 2018 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

A video-assisted thoracoscopic approach to lobectomy varies among surgeons. Typically, 3 to 4 incisions are made. Our approach has evolved from a 3-port to a 2-port approach to a single 4- to 5-cm incision with no rib spreading. We report results with single-incision video-assisted thoracic major pulmonary resections during our first 2 years of experience.In June 2010, we began performing video-assisted thoracoscopic lobectomies through a uniportal approach (no rib spreading). By July 12, 2012, 102 patients had undergone this single-incision approach.Of 102 attempted major resections, 97 were successfully completed with a single incision (operations in 3 patients were converted to open surgery and 2 patients needed 1 additional incision). Five uniportal pneumonectomies were not included in the study. We have analyzed early outcomes of successful uniportal lobectomies (92 patients studied). Right upper lobectomy was the most frequent resection (28 cases). Mean surgical time was 154.1 ± 46 minutes (range, 60-310 minutes), mean number of lymph nodes was 14.5 ± 7 (range, 5-38 nodes), and mean number of explored nodal stations was 4.6 ± 1.2 (range, 3-8 stations). The mean tumor size was 2.8 ± 1.5 cm (0-6.5 cm). The median duration of time a chest tube was in place was 2 days and the median length of hospital stay was 3 days. There were complications in 14 patients; no postoperative 30-day mortality was reported.Single-incision video-assisted thoracoscopic anatomic resection is a feasible and safe procedure with good perioperative results, especially when performed by surgeons experienced with the double-port technique and anterior thoracotomy.Copyright © 2013 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

The solitary pulmonary nodule (SPN) is a frequent incidental finding that may represent primary lung cancer or other malignant or benign lesions. The optimal management of the SPN remains unclear.We conducted a systematic literature review to address the following questions: (1) the prevalence of SPN; (2) the prevalence of malignancy in nodules with varying characteristics (size, morphology, and type of opacity); (3) the relationships between growth rates, histology, and other nodule characteristics; and (4) the performance characteristics and complication rates of tests for SPN diagnosis. We searched MEDLINE and other databases and used previous systematic reviews and recent primary studies.Eight large trials of lung cancer screening showed that both the prevalence of at least one nodule (8 to 51%) and the prevalence of malignancy in patients with nodules (1.1 to 12%) varied considerably across studies. The prevalence of malignancy varied by size (0 to 1% for nodules < 5 mm, 6 to 28% for nodules 5 to 10 mm, and 64 to 82% for nodules > 20 mm). Data from six studies of patients with incidental or screening-detected nodules showed that the risk for malignancy was approximately 20 to 30% in nodules with smooth edges; in nodules with irregular, lobulated, or spiculated borders, the rate of malignancy was higher but varied across studies from 33 to 100%. Nodules that were pure ground-glass opacities were more likely to be malignant (59 to 73%) than solid nodules (7 to 9%). The sensitivity of positron emission tomography imaging for identifying a malignant SPN was consistently high (80 to 100%), whereas specificity was lower and more variable across studies (40 to 100%). Dynamic CT with nodule enhancement yielded the most promising sensitivity (sensitivity, 98 to 100%; specificity, 54 to 93%) among imaging tests. In studies of CT-guided needle biopsy, nondiagnostic results were seen approximately 20% of the time, but sensitivity and specificity were excellent when biopsy yielded a specific benign or malignant result.The prevalence of an SPN and the prevalence of malignancy in patients with an SPN vary widely across studies. The interpretation of these variable prevalence rates should take into consideration not only the nodule characteristics but also the population at risk. Modern imaging tests and CT-guided needle biopsy are highly sensitive for identifying a malignant SPN, but the specificity of imaging tests is variable and often poor.

 We aimed to identify clinicopathologic characteristics and risk of invasiveness of lung adenocarcinoma in surgically resected pure ground-glass opacity lung nodules (GGNs) smaller than 2 cm. Among 755 operations for lung cancer or tumors suspicious for lung cancer performed from 2012 to 2016, we retrospectively analyzed 44 surgically resected pure GGNs smaller than 2 cm in diameter on computed tomography (CT). The study group was composed of 36 patients including 11 men and 25 women with a median age of 59.5 years (range, 34-77). Median follow-up duration of pure GGNs was 6 months (range, 0-63). Median maximum diameter of pure GGNs was 8.5 mm (range, 4-19). Pure GGNs were resected by wedge resection, segmentectomy, or lobectomy in 27 (61.4%), 10 (22.7%), and 7 (15.9%) cases, respectively. Pathologic diagnosis was atypical adenomatous hyperplasia, adenocarcinoma in situ, minimally invasive adenocarcinoma (MIA), or invasive adenocarcinoma (IA) in 1 (2.3%), 18 (40.9%), 15 (34.1%), and 10 (22.7%) cases, respectively. The optimal cutoff value for CT-maximal diameter to predict MIA or IA was 9.1 mm. In multivariate analyses, maximal CT-maximal diameter of GGNs ≥10 mm (odds ratio, 24.050; 95% confidence interval, 2.6-221.908;  = 0.005) emerged as significant independent predictor for either MIA or IA. Estimated risks of MIA or IA were 37.2, 59.3, 78.2, and 89.8% at maximal GGN diameters of 5, 10, 15, and 20 mm, respectively. Pure GGNs were highly associated with lung adenocarcinoma in surgically resected cases, while estimated risk of GGNs invasiveness gradually increased as maximal diameter increased.Georg Thieme Verlag KG Stuttgart · New York.

To determine the presence and morphology of subsolid pulmonary nodules (SSNs) in a non-screening setting and relate them to clinical and patient characteristics.A total of 16,890 reports of clinically obtained chest CT (06/2011 to 11/2014, single-centre) were searched describing an SSN. Subjects with a visually confirmed SSN and at least two thin-slice CTs were included. Nodule volumes were measured. Progression was defined as volume increase exceeding the software interscan variation. Nodule morphology, location, and patient characteristics were evaluated.Fifteen transient and 74 persistent SSNs were included (median follow-up 19.6 [8.3-36.8] months). Subjects with an SSN were slightly older than those without (62 vs. 58 years; p = 0.01), but no gender predilection was found. SSNs were mostly located in the upper lobes. Women showed significantly more often persistent lesions than men (94 % vs. 69 %; p = 0.002). Part-solid lesions were larger (1638 vs. 383 mm; p < 0.001) and more often progressive (68 % vs. 38 %; p = 0.02), compared to pure ground-glass nodules. Progressive SSNs were rare under the age of 50 years. Logistic regression analysis did not identify additional nodule parameters of future progression, apart from part-solid nature.This study confirms previously reported characteristics of SSNs and associated factors in a European, routine clinical population.• SSNs in women are significantly more often persistent compared to men. • SSN persistence is not associated with age or prior malignancy. • The majority of (persistent) SSNs are located in the upper lung lobes. • A part-solid nature is associated with future nodule growth. • Progressive solitary SSNs are rare under the age of 50 years.

The purpose of this study was to evaluate the natural evolution of ground-glass nodules (GGNs) in the Multicentric Italian Lung Detection (MILD) trial, which adopted a nonsurgical approach to this subset of lesions.From September 2005 to August 2007, 56 consecutive MILD participants with 76 GGNs were identified from 1866 individuals who underwent baseline low-dose computed tomography. The features of GGNs were assessed and compared with the corresponding repeat low-dose computed tomographies after a mean time of 50.26 ± 7.3 months. The GGNs were classified as pure (pGGN) or part-solid (psGGN) GGNs. The average of the maximum and the minimum diameters for both pGGNs and psGGNs and the maximum diameter of the solid portion of psGGNs were manually measured. At follow-up, GGNs were classified as follows: resolved, decreased, stable, or progressed (according to three defined growth patterns).A total of 15 of 48 pGGNs (31.3%) resolved, 4 of 48 (8.3%) decreased in size, 21 of 48 (43.8%) remained stable, and 8 of 48 (16.7%) progressed. Among the psGGNs with a solid component smaller than 5 mm, 3 of 26 (11.5%) resolved, 11 of 26 (42.3%) remained stable, and 12 of 26 (46.2%) progressed. One of the two psGGNs with a solid component larger than 5 mm remained stable, and the other decreased in size. Four lung cancers were detected among the GGN subjects, but only one arose from a psGGN, and was resected in stage Ia.The progression rate of the GGNs toward clinically relevant disease was extremely low in the MILD trial and supports an active surveillance attitude.

To evaluate CT and histopathologic features of lung adenocarcinoma with pure ground-glass nodule (pGGN) ≤10 mm in diameter.CT appearances of 148 patients (150 lesions) who underwent curative resection of lung adenocarcinoma with pGGN ≤10 mm (25 atypical adenomatous hyperplasias, 42 adenocarcinoma in situs, 38 minimally invasive adenocarcinomas, and 45 invasive pulmonary adenocarcinomas) were analyzed for lesion size, density, bubble-like sign, air bronchogram, vessel changes, margin, and tumour-lung interface. CT characteristics were compared among different histopathologic subtypes. Univariate and multivariate analysis were used to assess the relationship between CT characteristics of pGGN and lesion invasiveness, respectively.There were statistically significant differences among histopathologic subtypes in lesion size, vessel changes, and tumour-lung interface (P<0.05). Univariate analysis revealed significant differences of vessel changes, margin and tumour-lung interface between preinvasive and invasive lesions (P<0.05). Logistic regression analysis showed that the vessel changes, unsmooth margin and clear tumour-lung interface were significant predictive factors for lesion invasiveness, with odds ratios (95% CI) of 2.57 (1.17-5.62), 1.83 (1.25-2.68) and 4.25 (1.78-10.14), respectively.Invasive lesions are found in 55.3% of subcentimeter pGGNs in our cohort. Vessel changes, unsmooth margin, and clear lung-tumour interface may indicate the invasiveness of lung adenocarcinoma with subcentimeter pGGN.• Invasive lesions were found in 55.3% of lung adenocarcinomas with subcentimeter pGGNs • Lesion size, vessel changes, and tumour-lung interface showed different among histopathologic subtypes • Vessel changes, unsmooth margin and clear tumour-lung interface were predictors for lesion invasiveness.

The Fleischner Society Guidelines for management of solid nodules were published in 2005, and separate guidelines for subsolid nodules were issued in 2013. Since then, new information has become available; therefore, the guidelines have been revised to reflect current thinking on nodule management. The revised guidelines incorporate several substantive changes that reflect current thinking on the management of small nodules. The minimum threshold size for routine follow-up has been increased, and recommended follow-up intervals are now given as a range rather than as a precise time period to give radiologists, clinicians, and patients greater discretion to accommodate individual risk factors and preferences. The guidelines for solid and subsolid nodules have been combined in one simplified table, and specific recommendations have been included for multiple nodules. These guidelines represent the consensus of the Fleischner Society, and as such, they incorporate the opinions of a multidisciplinary international group of thoracic radiologists, pulmonologists, surgeons, pathologists, and other specialists. Changes from the previous guidelines issued by the Fleischner Society are based on new data and accumulated experience. RSNA, 2017 Online supplemental material is available for this article. An earlier incorrect version of this article appeared online. This article was corrected on March 13, 2017.

A clinical prediction model to identify malignant nodules based on clinical data and radiological characteristics of lung nodules was derived using logistic regression from a random sample of patients (n = 419) and tested on data from a separate group of patients (n = 210).To use multivariate logistic regression to estimate the probability of malignancy in radiologically indeterminate solitary pulmonary nodules (SPNs) in a clinically relevant subset of patients with SPNs that measured between 4 and 30 mm in diameter.A retrospective cohort study at a multispecialty group practice included 629 patients (320 men, 309 women) with newly discovered (between January 1, 1984, and May 1, 1986) 4- to 30-mm radiologically indeterminate SPNs on chest radiography. Patients with a diagnosis of cancer within 5 years prior to the discovery of the nodule were excluded. Clinical data included age, sex, cigarette-smoking status, and history of extrathoracic malignant neoplasm, asbestos exposure, and chronic interstitial or obstructive lung disease; chest radiological data included the diameter, location, edge characteristics (eg, lobulation, spiculation, and shagginess), and other characteristics (eg, cavitation) of the SPNs. Predictors were identified in a random sample of two thirds of the patients and tested in the remaining one third.Sixty-five percent of the nodules were benign, 23% were malignant, and 12% were indeterminate. Three clinical characteristics (age, cigarette-smoking status, and history of cancer [diagnosis, > or = 5 years ago]) and 3 radiological characteristics (diameter, spiculation, and upper lobe location of the SPNs) were independent predictors of malignancy. The area (+/-SE) under the evaluated receiver operating characteristic curve was 0.8328 +/- 0.0226.Three clinical and 3 radiographic characteristics predicted the malignancy in radiologically indeterminate SPNs.

Estimating the clinical probability of malignancy in patients with a solitary pulmonary nodule (SPN) can facilitate the selection and interpretation of subsequent diagnostic tests.We used multiple logistic regression analysis to identify independent clinical predictors of malignancy and to develop a parsimonious clinical prediction model to estimate the pretest probability of malignancy in a geographically diverse sample of 375 veterans with SPNs. We used data from Department of Veterans Affairs (VA) administrative databases and a recently completed VA Cooperative Study that evaluated the accuracy of positron emission tomography (PET) scans for the diagnosis of SPNs.The mean (+/- SD) age of subjects in the sample was 65.9 +/- 10.7 years. The prevalence of malignant SPNs was 54%. Most participants were either current smokers (n = 177) or former smokers (n = 177). Independent predictors of malignant SPNs included a positive smoking history (odds ratio [OR], 7.9; 95% confidence interval [CI], 2.6 to 23.6), older age (OR, 2.2 per 10-year increment; 95% CI, 1.7 to 2.8), larger nodule diameter (OR, 1.1 per 1-mm increment; 95% CI, 1.1 to 1.2), and time since quitting smoking (OR, 0.6 per 10-year increment; 95% CI, 0.5 to 0.7). Model accuracy was very good (area under the curve of the receiver operating characteristic, 0.79; 95% CI, 0.74 to 0.84), and there was excellent agreement between the predicted probability and the observed frequency of malignant SPNs.Our prediction rule can be used to estimate the pretest probability of malignancy in patients with SPNs, and thereby facilitate clinical decision making when selecting and interpreting the results of diagnostic tests such as PET imaging.

We aimed to prospectively evaluate our previously proposed selective mediastinal lymph node (LN) dissection strategy for peripheral clinical T1N0 invasive non-small cell lung cancer (NSCLC).This is a multicenter, prospective clinical trial in China. We set six criteria for predicting negative LN stations and finally guiding selective LN dissection. Consolidation tumor ratio ≤ 0.5, segment location, lepidic predominant adenocarcinoma (LPA), negative hilar nodes (stations 10/11/12) and negative visceral pleural invasion (VPI) were used separately or in combination as predictors of negative LN status in the whole, superior or inferior mediastinal zone. LPA, hilar nodes involvement and VPI were diagnosed intraoperatively. All patients actually underwent systematic mediastinal LN dissection. The primary endpoint was the accuracy of the strategy in predicting LN involvement. If LN metastasis occurred in certain mediastinal zone that was predicted to be negative, it was considered as an "inaccurate" case.A total of 720 patients were enrolled. The median number of LN dissected was 15 (interquartile range: 11-20). All negative node status in certain mediastinal zone was correctly predicted by the strategy. Compared to final pathology, the accuracy of frozen section to diagnose LPA, VPI and hilar nodes metastasis was 94.0%, 98.9%, and 99.6%, respectively. Inaccurate intraoperative diagnosis of LPA, VPI or hilar nodes metastasis did not lead to inaccurate prediction of node negative status.This is the first prospective trial validating the specific mediastinal LN metastasis pattern in cT1N0 invasive NSCLC, which provides important evidence for clinical applications of selective LN dissection strategy.Copyright © 2023 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

With the widespread implementation of lung cancer screening, more and more patients are being diagnosed with multiple primary lung cancers (MPLCs). In the era of precision medicine, many controversies remain in differentiating MPLCs from intrapulmonary metastasis and the optimum treatment choice, especially in patients exhibiting similar histology. In this review, we summarize common diagnostic criteria and novel discrimination methods with a special emphasis on the emerging value of broad panel next-generation sequencing (NGS) for the diagnosis of MPLCs. We then discuss current advances regarding therapeutic approaches for MPLCs. Radical surgery is the main treatment modality, while stereotactic body radiotherapy (SBRT) is safe and feasible for early-stage MPLC patients with inoperable tumors. In addition, immunotherapy and targeted therapy, particularly epidermal growth factor receptor-tyrosine kinase inhibitors, are emerging therapeutic strategies that are still in their infancy. Characteristics of both genomic profiles and tumor microenvironment are currently being evaluated but warrant further exploration to facilitate the application of targeted systematic therapies in MPLC patients.© 2020 Zhao et al.

Our previous animal and preliminary human studies indicated that bronchoscopy-guided cooled radiofrequency ablation (RFA) for the lung is a safe and feasible procedure without major complications.The present study was performed to evaluate the safety, effectiveness and feasibility of computed tomography (CT)-guided bronchoscopy cooled RFA in patients with medically inoperable non-small-cell lung cancer (NSCLC).Patients with pathologically diagnosed NSCLC, who had no lymph node involvement or distant metastases (T1-2aN0M0) but were not surgical candidates because of comorbidities (e.g., synchronous multiple nodules, advanced age, cardiovascular disease, poor pulmonary function, etc.) were enrolled in the present study. The diagnosis and location between the nearest bronchus and target tumor were made by CT-guided bronchoscopy before the treatment. A total of 28 bronchoscopy-guided cooled RFA procedures were performed in 20 patients. After treatment, serial CT imaging was performed as follow-up.Eleven lesions showed significant reductions in tumor size and 8 lesions showed stability, resulting in a local control rate of 82.6%. The median progression-free survival was 35 months (95% confidence interval: 22-45 months), and the 5-year overall survival was 61.5% (95% confidence interval: 36-87%). Three patients developed an acute ablation-related reaction (fever, chest pain) and required hospitalization but improved with conservative treatment. There were no other adverse events in the present study.CT-guided bronchoscopy cooled RFA is applicable for only highly selected subjects; however, our trial may be an alternative strategy, especially for disease local control in medically inoperable patients with stage I NSCLC.

We have recently developed a flexible catheter electrode used for bronchoscopic radiofrequency ablation (RFA). Two patients with nonsurgical stage IA peripheral lung cancer and 1 with lung metastasis underwent treatment with flexible catheter RFA utilizing navigation bronchoscopy. Chest computed tomography (CT) and positron emission tomography/CT (PET/CT) were performed before and after RFA to assess the ablation response of the patients. One patient's tumor had no prior PET uptake and therefore no follow-up PET was obtained. The first and the third patient obtained partial response to RFA, and the second patient obtained complete response 3 months after RFA. The first patient developed progressive disease 6 months after RFA. The second and the third patient achieved one-year progression-free survival. No significant complications occurred in the 3 patients. Navigation bronchoscopy-guided RFA is a safe and feasible procedure for poor surgical candidates with stage IA lung cancer or lung metastasis.© 2017 S. Karger AG, Basel.

To evaluate the possibility of pathologic diagnosis and genetic analysis of percutaneous core-needle biopsy (CNB) lung tumor specimens obtained immediately after radiofrequency ablation (RFA).Patients who underwent CNB of lung tumors immediately after RFA from May 2013 to May 2016 were analyzed. There were 19 patients (8 men and 11 women; median age, 69 years; range, 52-88 years) and 19 lung tumors measuring 0.5-2.6 cm (median, 1.6 cm). Thirteen tumors were solid, and 6 were predominantly ground-glass opacity (GGO) on computed tomography. All specimens were pathologically examined using hematoxylin and eosin (H&E) staining and additional immunostaining, as necessary. The specimens were analyzed for EGFR and KRAS genetic mutations. The safety and technical success rate of the procedure and the possibility of pathologic diagnosis and genetic mutation analysis were evaluated.Major and minor complication rates were 11% (2/19) and 53% (10/19), respectively. Tumor cells were successfully obtained in 16 cases (84%, 16/19), and technical success rate was significantly lower for GGO-dominant tumors (50%, 3/6) compared with solid lesions (100%, 13/13, p = 0.02). Pathologic diagnosis was possible in 79% (15/19) of cases based on H&E staining alone (n = 12) and with additional immunostaining (n = 3). Although atypical cells were obtained, pathologic diagnosis could not be achieved in 1 case (5%, 1/19). Both EGFR and KRAS mutations could be analyzed in 74% (14/19) of the specimens.Pathologic diagnosis and genetic analysis could be performed even for lung tumor specimens obtained immediately after RFA.

The objective of this study is to determine the diagnostic ability of percutaneous core biopsy immediately after microwave ablation (MWA) for lung ground-glass opacity (GGO).Seventy-four patients with 74 lung GGOs were enrolled and treated with MWA. A percutaneous core needle biopsy was performed pre- and immediately post-MWA. All biopsy specimens were histologically examined by hematoxylin and eosin staining and immunostaining. Histologically, atypical adenomatous hyperplasia (AAH), adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA), and invasive adenocarcinoma (AC) were identified as positive, while chronic inflammation or normal lung tissue was identified as negative.The outcomes of pre-MWA histological diagnosis were AAH (n = 4), AIS (n = 16), MIA (n = 14), AC (n = 29), chronic inflammation (n = 2), and lung tissue (n = 9) with an 85.1% (63/74) positive diagnosis rate. The outcomes of the immediately post-MWA histological diagnosis were AAH (n = 5), AIS (n = 10), MIA (n = 11), AC (n = 29), chronic inflammation (n = 1), and lung tissue (n = 18) with a 74.3% (55/74) positive diagnosis rate. There was no significant difference in the positive diagnosis rate between the pre- and immediately post-MWA groups (P = 0.10). The outcomes of the combined diagnosis of pre- and immediately post-MWA were AAH (n = 4), AIS (n = 16), MIA (n = 16), AC (n = 31), chronic inflammation (n = 2), and lung tissue (n = 5) with a positive diagnosis rate of 90.5% (67/74), which was higher than that by pre-MWA biopsy (P < 0.05). The main complications were pneumothorax (n = 45, 60.8%), hemoptysis (n = 24, 32.4%), pleural effusion (n = 39, 52.7%), and pulmonary infection (n = 10, 13.5%).Immediately post-MWA core biopsy has promising efficacy for histological diagnosis of lung GGOs.

To evaluate the feasibility, safety, and diagnostic performance of sequential core-needle biopsy (CNB) technique following coaxial low-power microwave thermal coagulation (MTC) for ground-glass opacity (GGO) nodules.From December 2017 to July 2019, a total of 32 GGOs (with diameter of 12 ± 4 mm) in 31 patients received two times of CNBs, both prior to and immediately after MTC at a power of 20 watts. The frequency and type of complications associated with CNBs were examined. The pathologic diagnosis and genetic analysis were performed for specimens obtained from the two types of biopsy.The technical success rates of pre- and post-MTC CNBs were 94% and 100%, respectively. The complication rate was significantly lower with post-MTC CNB as compared to pre-MTC CNB (42% versus 97%, p < 0.001). Larger amount of specimens could be obtained by post-MTC CNB. The pathological diagnosis rate of post-MTC CNB was significantly higher than that of pre-MTC CNB (100% versus 75%, p = 0.008), whereas the success rates of genetic analysis were comparable between the two groups (100% versus 84%, p = 0.063). Regular ablation could be further performed after post-MTC CNB to achieve local tumor control.Sequential biopsy following coaxial low-power MTC can reduce the risk of complications and provide high-quality specimens for pulmonary GGOs. Combining this technique with standard ablation allows for simultaneous diagnosis and treatment within a single procedure.