Pulmonary Hamartoma Associated With Lung Cancer (PHALC Study): Results of a Multicenter Study.

PURPOSE: Pulmonary hamartoma is the most common benign tumor of the lung. We analyzed a 20-year historical series of patients with pulmonary hamartoma undergoing surgical resection, aiming to evaluate the characteristics, the outcomes, and the association between hamartoma and lung cancer. METHODS: It was a retrospective multicenter study including the data of all consecutive patients with pulmonary hamartoma undergoing surgical resection. The end-points were to evaluate: (i) the characteristics of hamartoma, (ii) outcomes, and (iii) whether hamartoma was a predictive factor for lung cancer development RESULTS: Our study population included 540 patients. Upfront surgical or endoscopic resection was performed in 385 (71%) cases while in the remaining 155 (29%) cases, the lesions were resected 20 ± 3.5 months later due to increase in size. In most cases, lung sparing resection was carried out including enucleation (n = 259; 48%) and wedge resection (n = 230; 43%) while 5 (1%) patients underwent endoscopic resection. Only two patients (0, 2%) had major complications. One patient (0.23%) had recurrence after endoscopic resection, while no cases of malignant degeneration were seen (mean follow-up:103.3 ± 93 months). Seventy-six patients (14%) had associated lung cancer, synchronous in 9 (12%) and metachronous in 67 (88%). Only age > 70-year-old (p = 0.0059) and smokers > 20 cigarettes/day (p < 0.0001) were the significant risk factors for lung cancer. CONCLUSION: PH was a benign tumor, with no evidence of recurrence and/or of malignant degeneration after resection. The association between hamartoma and lung cancer was a spurious phenomenon due to common risk factors.

Correlation between CT findings and thoracoscopic diagnosis in diffuse pleural disease.

OBJECTIVE: Computed Tomography (CT) is considered part of the routine diagnostic workup for pleural malignancy. The definitive diagnosis of pleural malignancy depends upon histological confirmation by pleural biopsy. The aim of this study is to assess the sensitivity and specificity of CT, in view of the latest imaging technologies, in detecting pleural malignancy compared to definitive histology achieved via thoracoscopy (VATS). MATERIALS AND METHODS: We included in this retrospective study 90 patients (36 F, 54 M) with suspected pleural malignancy  evaluated in our Institution with CT scan who received a definitive diagnosis after VATS biopsy. Unaware of histopathologic diagnoses CT scans were evaluated by a junior and two experts thoracic radiologist. Conclusions were reached by consensus. RESULTS: We evaluated all CT signs suggestive for malignant pleural diseases: pleural thickening > 10 mm (Se 0,41 , Sp 0,79); nodular thickening (Se 0,86, Sp 0,75); circumferential thickening (Se 0,79, Sp 0,69); irregular pleural thickening (Se 0,77, Sp 0,91); mediastinal involvement (Se 0,88, Sp 0,64); costal involvement (Se 0,89, Sp 0,60); diaphragmatic involvement (Se 0,88, Sp 0,53). Furthermore, the diagnostic performance of additional CT features was evaluated: concomitant costal, mediastinal and diaphragmatic pleura lesions (Se 0,84, Sp 0,69); nodular/irregular thickening with mediastinal pleural involvement (Se 0,83, Sp 0,90); nodular/irregular thickening with diaphragmatic pleural involvement (Se 0,81, Sp 0,90). CONCLUSIONS: CT confirms its central role in the pleura malignancy. The high sensibility, respect to previous studies, especially in the presence of nodular pleural thickening, may lead to reconsider at least partly the diagnostic pathway of diffuse pleural disease, avoiding the use of VATS in patients not eligible for surgery, in favor of US or CT guided core biopsy.

Prognostic factors of lung cancer in lymphoma survivors (the LuCiLyS study).

BACKGROUND: Second cancer is the leading cause of death in lymphoma survivors, with lung cancer representing the most common solid tumor. Limited information exists about the treatment and prognosis of second lung cancer following lymphoma. Herein, we evaluated the outcome and prognostic factors of Lung Cancer in Lymphoma Survivors (the LuCiLyS study) to improve the patient selection for lung cancer treatment. METHODS: This is a retrospective multicentre study including consecutive patients treated for lymphoma disease that subsequently developed non-small cell lung cancer (NSCLC). Data regarding lymphoma including age, symptoms, histology, disease stage, treatment received and lymphoma status at the time of lung cancer diagnosis, and data on lung carcinoma as age, smoking history, latency from lymphoma, symptoms, histology, disease stage, treatment received, and survival were evaluated to identify the significant prognostic factors for overall survival. RESULTS: Our study population included 164 patients, 145 of which underwent lung cancer resection. The median overall survival was 63 (range, 58-85) months, and the 5-year survival rate 54%. At univariable analysis no-active lymphoma (HR: 2.19; P=0.0152); early lymphoma stage (HR: 1.95; P=0.01); adenocarcinoma histology (HR: 0.59; P=0.0421); early lung cancer stage (HR: 3.18; P<0.0001); incidental diagnosis of lung cancer (HR: 1.71; P<0.0001); and lung cancer resection (HR: 2.79; P<0.0001) were favorable prognostic factors. At multivariable analysis, no-active lymphoma (HR: 2.68; P=0.004); early lung cancer stage (HR: 2.37; P<0.0001); incidental diagnosis of lung cancer (HR: 2.00; P<0.0001); and lung cancer resection (HR: 2.07; P<0.0001) remained favorable prognostic factors. Patients with non-active lymphoma (n=146) versus those with active lymphoma (n=18) at lung cancer diagnosis presented better median survival (64 vs. 37 months; HR: 2.4; P=0.02), but median lung cancer specific survival showed no significant difference (27 vs. 19 months; HR: 0.3; P=0.17). CONCLUSIONS: The presence and/or a history of lymphoma should not be a contraindication to resection of lung cancer. Inclusion of lymphoma survivors in a lung cancer-screening program may lead to early detection of lung cancer, and improve the survival.

Potential Diagnostic and Prognostic Role of Microenvironment in Malignant Pleural Mesothelioma.

INTRODUCTION: A comprehensive analysis of the immune cell infiltrate collected from pleural fluid and from biopsy specimens of malignant pleural mesothelioma (MPM) may contribute to understanding the immune-evasion mechanisms related to tumor progression, aiding in differential diagnosis and potential prognostic stratification. Until now such approach has not routinely been verified. METHODS: We enrolled 275 patients with an initial clinical diagnosis of pleural effusion. Specimens of pleural fluids and pleural biopsy samples used for the pathologic diagnosis and the immune phenotype analyses were blindly investigated by multiparametric flow cytometry. The results were analyzed using the Kruskal-Wallis test. The Kaplan-Meier and log-rank tests were used to correlate immune phenotype data with patients' outcome. RESULTS: The cutoffs of intratumor T-regulatory (>1.1%) cells, M2-macrophages (>36%), granulocytic and monocytic myeloid-derived suppressor cells (MDSC; >5.1% and 4.2%, respectively), CD4 molecule-positive (CD4+) programmed death 1-positive (PD-1+) (>5.2%) and CD8+PD-1+ (6.4%) cells, CD4+ lymphocyte activating 3-positive (LAG-3+) (>2.8% ) and CD8+LAG-3+ (>2.8%) cells, CD4+ T cell immunoglobulin and mucin domain 3-positive (TIM-3+) (>2.5%), and CD8+TIM-3+ (>2.6%) cells discriminated MPM from pleuritis with 100% sensitivity and 89% specificity. The presence of intratumor MDSC contributed to the anergy of tumor-infiltrating lymphocytes. The immune phenotype of pleural fluid cells had no prognostic significance. By contrast, the intratumor T-regulatory and MDSC levels significantly correlated with progression-free and overall survival, the PD-1+/LAG-3+/TIM-3+ CD4+ tumor-infiltrating lymphocytes correlated with overall survival. CONCLUSIONS: A clear immune signature of pleural fluids and tissues of MPM patients may contribute to better predict patients' outcome.

Risk of recurrence in stage I adenocarcinoma of the lung: a multi-institutional study on synergism between type of surgery and type of nodal staging.

BACKGROUND: In last years, an increasing interest emerges on the role of sub-lobar resection and lobe-specific lymph nodal dissection in the treatment of early-stage lung cancer. The aim of our study was to define the impact on cumulative incidence of recurrence (CIR) of type of surgical resection and type of nodal staging in this subset of patients. Furthermore, we evaluated the possible synergism between the different kinds of procedure. METHODS: An analysis of 969 consecutive stage I pulmonary adenocarcinoma patients, operated in six Thoracic Surgery Institutions between 2001 and 2013, was conducted. Type of surgical resection included lobectomy and sub-lobar resection; while pneumonectomy and bilobectomy were excluded from the analysis. Nodal staging procedures were classified in nodal sampling (NS), lobe-specific lymph node dissection (LS-ND) and systematic lymph node dissection (SND). Multivariable-adjusted comparisons for CIR was performed using Fine and Grey model, taking into account of death by any cause as competing event. In order to evaluate synergism between the different procedures, the test of interaction between type of surgical resection and type of nodal staging was carried out and results presented in a stratified way. RESULTS: Eight-hundred forty-six (87%) patients were submitted to lobectomy, while 123 (13%) to sub-lobar resection. Four-hundred fifty-five (47%) patients received SND, 98 (10%) LS-ND and 416 (43%) NS. Two-hundred forty-seven (26%) patients developed a local/distant recurrence with a 5-year CIR of 24.2%. Multivariable-adjusted comparisons showed an independent negative effect of sub-lobar resection (HR =1.52; 95% CI: 1.07-2.17), LS-ND (HR =1.74; 95% CI: 1.16-2.6) and NS (HR =1.49; 95% CI: 1.12-1.98) on CIR. Test of interaction showed a homogeneity of results among subgroups. CONCLUSIONS: Patients affected by stage I pulmonary adenocarcinoma and submitted to lobectomy presented a significant lower recurrence rate than those submitted to sub-lobar resection. Moreover, SND presented an independent positive effect on recurrence development than other lymph node assessment strategy. Finally, lobectomy in combination with systematic lymph nodal resection showed the best results in term of CIR.

Anatomical resections are superior to wedge resections for overall survival in patients with Stage 1 typical carcinoids.

OBJECTIVES: Typical carcinoids (TCs) are rare, slow-growing neoplasms, usually characterized by satisfactory surgical outcomes. Due to the rarity of TCs, international guidelines for the management of particular clinical presentations currently do not exist. In particular, non-anatomical resections (wedges) are sometimes advocated for Stage 1 TCs because of their indolent behaviour. The aim of this paper was to evaluate the most effective type of surgery for Stage 1 TCs, using the European Society of Thoracic Surgeons retrospective database of the Neuroendocrine Tumors of the Lung Working Group. METHODS: We analysed the effect of surgical procedure on the survival of patients with Stage 1 TCs. Overall survival (OS) was calculated from the date of intervention. The cumulative incidence of cause-specific death (tumour- and non-tumour-related) was also estimated. The impact of the surgical procedure (i.e. lobectomy vs segmentectomy vs wedge resection) on survival was investigated using the Cox model with shared frailty (for OS, accounting for the within-centre correlation) and the Fine and Gray model (for cause-specific mortality) using the approach based on the multinomial propensity score. Effects were estimated including in the model the logit-transformed propensity scores of segmentectomy and wedge resection as covariates. RESULTS: A total of 876 patients with Stage 1 TCs (569 women, 65%) were included in this study. The median age was 60 years (interquartile range 47-69). At the last follow-up, 66 patients had died: The 5-year OS rate was 94.3% [95% confidence interval (CI) 92.2-95.9]. The 5-year cumulative incidences of tumour- and non-tumour-related deaths were 2.4% (95% CI 1.4-3.9) and 3.9% (95% CI 2.5-5.6%), respectively. The analysis performed using the multinomial propensity score approach confirmed the significantly worse survival of patients treated with a wedge resection compared to those treated with a lobectomy (hazard ratio 2.01, 95% CI 1.09-3.69; P = 0.024). Similar effects of wedge resection are detectable for cause-specific deaths: tumour-related (hazard ratio 2.28, 95% CI 0.86-6.02; P = 0.096) and non-tumour-related (hazard ratio 1.74, 95% CI 0.89-3.40; P = 0.105). CONCLUSIONS: In a large cohort of patients, we were able to demonstrate the superiority of anatomical surgical resection in Stage 1 TCs in terms of OS. This result should therefore be considered for future clinical guidelines for the management of TCs.

Individual data meta-analysis for the study of survival after pulmonary metastasectomy in colorectal cancer patients: A history of resected liver metastases worsens the prognosis.

OBJECTIVES: To assess the impact of a history of liver metastases on survival in patients undergoing surgery for lung metastases from colorectal carcinoma. METHODS: We reviewed recent studies identified by searching MEDLINE and EMBASE using the Ovid interface, with the following search terms: lung metastasectomy, pulmonary metastasectomy, lung metastases and lung metastasis, supplemented by manual searching. Inclusion criteria were that the research concerned patients with lung metastases from colorectal cancer undergoing surgery with curative intent, and had been published between 2007 and 2014. Exclusion criteria were that the paper was a review, concerned surgical techniques themselves (without follow-up), and included patients treated non-surgically. Using Stata 14, we performed aggregate data and individual data meta-analysis using random-effect and Cox multilevel models respectively. RESULTS: We collected data on 3501 patients from 17 studies. The overall median survival was 43 months. In aggregate data meta-analysis, the hazard ratio for patients with previous liver metastases was 1.19 (95% CI 0.90-1.47), with low heterogeneity (I2 4.3%). In individual data meta-analysis, the hazard ratio for these patients was 1.37 (95% CI 1.14-1.64; p < 0.001). Multivariate analysis identified the following factors significantly affecting survival: tumour-infiltrated pulmonary lymph nodes (p < 0.001), type of resection (p = 0.005), margins (p < 0.001), carcinoembryonic antigen levels (p < 0.001), and number and size of lung metastases (both p < 0.001). CONCLUSIONS: A history of liver metastases is a negative prognostic factor for survival in patients with lung metastases from colorectal cancer. We registered the meta-analysis protocol in PROSPERO (CRD42015017838).

Computed tomography of solitary fibrous tumor of the pleura abutting the mediastinum: A diagnostic challenge.

BACKGROUND: Solitary fibrous tumor of the pleura (SFTP) arising from the mediastinal pleura may be confused with primary mediastinal tumors. We studied the computerized tomographic (CT) findings of patients with SFTP that could suggest a diagnosis of SFTP. MATERIALS AND METHODS: At our hospital from January 1995 to June 2012, 39 patients with histologically confirmed SFTP were surgically treated; seven of them abutting the mediastinal pleura. The study group included seven patients aged between 53 and 81 years. Baseline CT scans were retrospectively reviewed to identify radiological findings suggestive of SFTP including: (1) smooth and sharply delineated contours; (2) obtuse, acute, or tapering angles between the lesion and the mediastinum depending on the size; (3) homogeneous soft-tissue attenuation; (4) "geographic pattern" due to the contemporary presence of large vessels, necrosis, and calcifications; (5) displacement of the lung parenchyma; (6) presence of a cleavage plane; and (7) absence of lymphadenopathy or pleural methastasis. RESULTS: All tumors formed acute angles with the pleura. Six out of the seven presented smoothly tapering margins, three had a "geographic pattern" of attenuation and displaced the anterior junction line; one showed an outside junction line development. Four cases had a clear pleural origin. CONCLUSIONS: The possibility of SFTP should be taken into account when a mass abuts the mediastinum projecting inside the thoracic cavity in the presence of an intense and "geographical pattern" of enhancement without lymphoadenopathy or pleural metastasis. These findings assume greater significance in the presence of discrepancy between the size of the lesion and the clinical presentation.

Assessing the prognostic impact of the International Association for the Study of Lung Cancer proposed definitions of complete, uncertain, and incomplete resection in non-small cell lung cancer surgery.

OBJECTIVE: The aim of this study was to assess the prognostic impact of the definitions of complete, uncertain, and incomplete resection in non-small cell lung cancer (NSCLC) surgery, as proposed by the International Association for the Study of Lung Cancer (IASLC). PATIENTS AND METHODS: Single institution retrospective study of consecutive patients undergoing surgery for NSCLC between 1998 and 2007. Complete resection was defined by absence of gross and microscopic residual disease; systematic nodal dissection; no extracapsular extension in distal lymph nodes; and negativity of the highest mediastinal node removed. An uncertain resection was defined by free resection margins, but one of the following applied: lymph node evaluation less rigorous than systematic nodal dissection; positivity of the highest mediastinal node removed; presence of carcinoma in situ at the bronchial margin; positive pleural lavage cytology. A resection was defined incomplete by presence of residual disease; extracapsular extension in distal lymph nodes; positive cytology of pleural or pericardial effusions. Follow-up was complete and all patients were followed up until death or for a minimum period of 5 years. Overall survival (OS) was analyzed using Kaplan-Meier method, log rank test, and Cox proportional hazards model. RESULTS: A total of 1277 patients were identified. One thousand and three patients (78.5%) underwent complete resection, 185 (14.5%) underwent uncertain resection, and 89 (7.0%) underwent incomplete resection. Both uncertain and incomplete resection were associated with significantly worse OS when compared with complete resection (hazard ratio: 1.69 and 3.18, respectively; both p=0.0001). Median OS and 5-year survival rate were 80.1, 39.9, 17.3 months and 58.8%, 37.3%, 15.7% in patients undergoing complete, uncertain, and incomplete resection, respectively. CONCLUSION: The present analysis suggests that in patients undergoing surgery for NSCLC, the IASLC definitions of complete, uncertain, and incomplete resection are associated with statistically significant differences in survival.

Diagnostic Imaging and workup of Malignant Pleural Mesothelioma.

Malignant pleural mesothelioma is the most frequent primary neoplasm of the pleura and its incidence is still increasing.This tumor has a strong association with exposure to occupational or environmental asbestos, often after a long latent period of 30-40 years.Plain chest radiography (CXR) is usually the first-line radiologic examination, but the radiographic findings are nonspecific due to its limited contrast resolution and they need to be complemented by other imaging modalities such as computed tomography (CT), magnetic resonance Imaging (MRI), Positron emission tomography-computed tomography (PET-CT) and ultrasound (US).The aim of this paper is to describe the imaging  features of this malignancy, underlining the peculiarity of CXR, CT, MRI, PET-CT and US and also focusing on diagnostic workup, based on the literature evidence and according to our experience.

Minute ventilation to carbon dioxide output (V'E/V'CO2 slope) is the strongest death predictor before larger lung resections.

The minute ventilation to CO2 production ratio (V'E/V'CO2 slope) was recently identified as a mortality predictor after lung surgery, but the effect of the resection extent was not taken into account.  The aim of this study was to investigate the role of V'E/V'CO2 slope as preoperative mortality predictor depending on the type of surgery performed. Retrospective analysis was performed on 263 consecutive patients evaluated before surgery for lung cancer. Death within 30 days and serious respiratory complications were considered. Univariate and multivariate regression analyses were used to identify independent predictors of death. Lobectomy or bilobectomy were performed in 186 patients with 29/186 (15.6%) serious pulmonary complications and 6/186 (3.2%) deaths. Pneumonectomy was performed in 77 patients with 14/77 (18.2%) serious complications and 5/77 (6.5%) deaths.  Considering the whole group, the peak oxygen consumption (V'02peak, L/ min; z=-2.66, p<0.008, OR 0.007) and V'E/V'C02 slope (z=2.80, p<0.005, OR 1.14) were independent predictors of mortality whereas in pneumonectomies V'E/V'C02 slope (z=2.34, p<0.02, OR 1.22) was the only independent predictor of mortality. High V'E/V'CO2 slope, age and low V'02peak are predictors of death and severe complications after lung surgery. Before larger resections as pneumonectomies an increased V'E/V'CO2 slope represents the best mortality predictor.

Apparent diffusion coefficient measurements in diffusion-weighted magnetic resonance imaging of the anterior mediastinum: inter-observer reproducibility of five different methods of region-of-interest positioning.

OBJECTIVES: To investigate inter-reader reproducibility of five different region-of-interest (ROI) protocols for apparent diffusion coefficient (ADC) measurements in the anterior mediastinum. METHODS: In eighty-one subjects, on ADC mapping, two readers measured the ADC using five methods of ROI positioning that encompassed the entire tissue (whole tissue volume [WTV], three slices observer-defined [TSOD], single-slice [SS]) or the more restricted areas (one small round ROI [OSR]), multiple small round ROI [MSR]). Inter-observer variability was assessed with interclass correlation coefficient (ICC), coefficient of variation (CoV), and Bland-Altman analysis. Nonparametric tests were performed to compare the ADC between ROI methods. The measurement time was recorded and compared between ROI methods. RESULTS: All methods showed excellent inter-reader agreement with best and worst reproducibility in WTV and OSR, respectively (ICC, 0.937/0.874; CoV, 7.3 %/16.8 %; limits of agreement, ±0.44/±0.77 × 10-3 mm2/s). ADC values of OSR and MSR were significantly lower compared to the other methods in both readers (p < 0.001). The SS and OSR methods required less measurement time (14 ± 2 s) compared to the others (p < 0.0001), while the WTV method required the longest measurement time (90 ± 56 and 77 ± 49 s for each reader) (p < 0.0001). CONCLUSIONS: All methods demonstrate excellent inter-observer reproducibility with the best agreement in WTV, although it requires the longest measurement time. KEY POINTS: • All ROI protocols show excellent inter-observer reproducibility. • WTV measurements provide the most reproducible ADC values. • ROI size and positioning influence ADC measurements in the anterior mediastinum. • ADC values of OSR and MSR are significantly lower than other methods. • OSR and WTV methods require the shortest and longest measurement time, respectively.

Radiological contribution to the diagnosis of early postoperative complications after lung resection for primary tumor: a revisional study.

In the post-operative course of the interventions of lung resection for primary tumor, complications of different nature and severity can arise, recognizing different pathogenetic mechanisms and differing according to the type of resection performed and to the time elapsed after surgery. The low diagnostic accuracy of chest radiography requires a thorough knowledge of the radiologist about all radiographic findings, both normal and pathological, which can be found in the immediate post-operative period (within 30 days after surgery). This article aims to describe the incidence, the clinical features and the radiological aspects of immediate complications following pulmonary resections, with specific reference to those in which the diagnostic imaging provides a fundamental contribution.

Sublobar resection versus lobectomy for stage I non-small cell lung cancer: an appropriate choice in elderly patients?

PURPOSES: The aim of this study was to evaluate whether sublobar resection could achieve recurrence and survival rates equivalent to lobectomy in high-risk elderly patients. METHODS: We conducted a retrospective multicenter study that including all consecutive patients (aged >75 years) who underwent operation for clinical stage I non-small cell lung cancer (NSCLC). The clinicopathological data, postoperative morbidity and mortality, recurrence rate and vital status were retrieved. The overall survival, cancer-specific survival and disease-free survival were also assessed. RESULTS: Two hundred and thirty-nine patients (median age 78 years) were enrolled. Lobectomies were performed in 149 (62.3 %) patients and sublobar resections in 90 (39 segmentectomies, 51 wedge resections). There were no differences in the recurrence rates following lobar versus sublobar resections (19 versus 23 %, respectively; p = 0.5) or the overall survival (p = 0.1), cancer-specific survival (p = 0.3) or disease-free survival (p = 0.1). After adjusting for 1:1 propensity score matching and a matched pair analysis, the results remained unchanged. A tumor size >2 cm and pN2 disease were independent negative prognostic factors in unmatched (p = 0.01 and p = 0.0003, respectively) and matched (p = 0.02 and p = 0.005, respectively) analyses. CONCLUSIONS: High-risk elderly patients may benefit from sublobar resection, which provides an equivalent long-term survival compared to lobectomy.

Diffusion-weighted quantitative MRI to diagnose benign conditions from malignancies of the anterior mediastinum: Improvement of diagnostic accuracy by comparing perfusion-free to perfusion-sensitive measurements of the apparent diffusion coefficient.

PURPOSE: To compare perfusion-free to perfusion-sensitive measurements of the apparent diffusion coefficient (ADC) to diagnose benign conditions from malignancies of the anterior mediastinum. MATERIALS AND METHODS: Seventy-six subjects were divided into a "benign conditions" group (A, n = 44) and a "malignancies" group (B, n = 32), based on histological findings. diffusion-weighted magnetic resonance imaging (DW-MRI) was performed at b of 0/150/800 sec/mm(2) . The ADCs were obtained on an ADC map by including (perfusion-sensitive = ADCb0-800 ) and excluding (perfusion-free = ADCb150-800 ) the b = 0 sec/mm(2) . The Mann-Whitney U-test was used to detect differences in ADCb0-800 compared with ADCb150-800 values between all cases, benign conditions, and malignancies. The same test was used to evaluate differences in ADCs between the two groups for each type of measurement (ADCb0-800 and ADCb150-800 ), and receiver-operating characteristic (ROC) curves were obtained to evaluate discrimination abilities with comparison of areas-under-ROC-curves (AUROC). Optimal cutpoints for discrimination between groups were determined by the Youden-Index with computation of accuracy. RESULTS: The median ADCb0-800 was significantly greater compared with ADCb150-800 for all cases (P = 0.0014), benign conditions (P = 0.0412), and malignancies (P = 0.0001). The median percentage of increase was 5.30% for group-A and 22.39% for group-B (P < 0.0001). AUROC of ADC in discriminating between groups was significantly greater for ADCb150-800 (0.932) compared with ADCb0-800 (0.831) (P = 0.001). The optimal cutpoint for distinction between groups was 1.52 × 10(-3) mm(2) /sec (sensitivity = 93.7%, specificity = 88.6%, accuracy = 90.8%) for ADCb150-800 and 1.75 × 10(-3) mm(2) /sec (sensitivity = 75.0%, specificity = 79.5%, accuracy = 77.6%) for ADCb0-800 . CONCLUSION: The use of perfusion-free ADC measurements significantly improves diagnostic accuracy of DW-MRI in differentiating benign conditions from malignancies of the anterior mediastinum. J. Magn. Reson. Imaging 2016;44:758-769.

Retrospective Multicenter Study Investigating the Role of Targeted Next-Generation Sequencing of Selected Cancer Genes in Mucinous Adenocarcinoma of the Lung.

INTRODUCTION: Mucin-rich lung adenocarcinomas (ADCs), namely mucinous and colloid ADCs, are classified as ADC variants according to the World Health Organization 2015 classification. A correlation between morphological patterns and mutational status of these rare entities is not well established. METHODS: We investigated the mutational profile of mucin-rich lung ADCs in correlation with histopathological and morphological features with the goal of identifying biological tumor characteristics of potential prognostic and therapeutic interest. A series of 54 surgically resected primary mucinous lung ADC samples were retrospectively analyzed for clinicopathological characteristics and by targeted next-generation sequencing. RESULTS: Fifty cases were invasive mucinous ADCs (32 pure and 18 mixed) and four were colloid-predominant ADCs. Invasive mucinous ADC cases with a pure mucinous pattern were associated with a lower risk of vascular invasion (p = 0.01), absence of signet ring cells (p = 0.03), negative nodal status (p = 0.006), and early clinical stage (p = 0.02). The most prevalent mutations involved the Kirsten rat sarcoma viral oncogene homolog gene (KRAS) and tumor protein p53 gene (TP53). Most mutations clustered in the mitogen-activated protein/protein kinase B pathway and in the p53/DNA repair pathway. A few uncommon epidermal growth factor receptor gene (EGFR) mutations were found. A correlation between a higher number of mutations and favorable clinical outcome was seen (p < 0.001). CONCLUSIONS: Our data showed that mucinous ADCs have peculiar pathological and molecular features that might suggest the need for a differentially tailored therapeutic approach compared with that to conventional lung ADC.

Safety and diagnostic performance of image-guided lung biopsy in the targeted therapy era.

OBJECTIVE OF THE STUDY: To identify risk factors for the adverse events and determine the diagnostic yield of a large series of image-guided thoracic biopsies performed in a single institution. MATERIALS AND METHODS: We reviewed a consecutive series of 811 patients (546 males; average age: 68 years.) who underwent 824 image-guided biopsies of pulmonary lesions performed between 2009 and 2013. Indications for biopsy were always evaluated by a multidisciplinary board. All complications were registered. The diagnostic accuracy was calculated on the basis of histology after surgery, response to medical therapy, or outcome at imaging follow-up. Safety and accuracy was correlated with patient-related and lesion-related factors. RESULTS: 61 biopsies were performed under US-guidance, 750 under CT-guidance, and 13 under combined guidance. The average lesion size was 36.4 mm (6-150 mm). FNAB was exclusively performed in 247 patients, whereas 577 patients underwent also or only core biopsy (CB). 40 (4.8 %) major complications and 172 (20.8 %) minor complications occurred. US-guidance, absence of perilesional emphysema and minor depth of the target lesion from the skin resulted as favorable predictors against major complications. According to the gold standard criteria, we demonstrated 497 true positives, 72 true negatives, 18 false negatives, 0 false positives. Sensitivity, specificity and diagnostic accuracy were 96.5, 100 and 97 %. No predictors for accuracy were found, but the number of samples largely related to the pathologist on site. CONCLUSIONS: Image-guided lung biopsy is safe and highly accurate for diagnosing thoracic lesions. In the targeted therapy era, CB with larger needles can be safely applied when the need for larger amounts of tumor tissue is presumed.

Prognostic model of survival for typical bronchial carcinoid tumours: analysis of 1109 patients on behalf of the European Association of Thoracic Surgeons (ESTS) Neuroendocrine Tumours Working Group.

OBJECTIVES: Typical carcinoids (TCs) are uncommon, slow-growing neoplasms, usually with high 5-year survival rates. As these are rare tumours, their management is still based on small clinical observations and no international guidelines exist. Based on the European Society of Thoracic Surgeon Neuroendocrine Tumours Working Group (NET-WG) Database, we evaluated factors that may influence TCs mortality. METHODS: Using the NET-WG database, an analysis on TC survival was performed. Overall survival (OS) was calculated starting from the date of intervention. Predictors of OS were investigated using the Cox model with shared frailty (accounting for the within-centre correlation). Candidate predictors were: gender, age, smoking habit, tumour location, previous malignancy, Eastern Cooperative Oncology Group (ECOG) performance status (PS), pT, pN, TNM stage and tumour vascular invasion. The final model included predictors with P ≤ 0.15 after a backward selection. Missing data in the evaluated predictors were multiple-imputed and combined estimates were obtained from five imputed data sets. RESULTS: For 58 of 1167 TC patients vital status was unavailable and analyses were therefore performed on 1109 patients from 17 institutions worldwide. During a median follow-up of 50 months, 87 patients died, with a 5-year OS rate of 93.7% (95% confidence interval: 91.7-95.3). Backward selection resulted in a prediction model for mortality containing age, gender, previous malignancies, peripheral tumour, TNM stage and ECOG PS. The final model showed a good discrimination ability with a C-statistic equal to 0.836 (bootstrap optimism-corrected 0.806). CONCLUSIONS: We presented and validated a promising prognostic model for TC survival, showing good calibration and discrimination ability. Further analyses are needed and could be focused on an external validation of this model.

Pulmonary metastasectomy in colorectal cancer patients with previously resected liver metastasis: pooled analysis.

BACKGROUND: Data addressing the outcomes and patterns of recurrence after pulmonary metastasectomy (PM) in patients with colorectal cancer (CRC) and previously resected liver metastasis are limited. METHODS: We searched the PubMed database for studies assessing PM in CRC and gathered individual data for patients who had PM and a previous curative liver resection. The influence of potential factors on overall survival (OS) was analyzed through univariate and multivariate analysis. RESULTS: Between 1983 and 2009, 146 patients from five studies underwent PM and had previous liver resection. The median interval from resection of liver metastasis until detection of lung metastasis and the median follow-up from PM were 23 and 48 months, respectively. Five-year OS and recurrence-free survival rates calculated from the date of PM were 54.4 and 29.3 %, respectively. Factors predicting inferior OS in univariate analysis included thoracic lymph node (LN) involvement and size of largest lung nodule ≥2 cm. Adjuvant chemotherapy and whether lung metastasis was detected synchronous or metachronous to liver metastasis had no influence on survival. In multivariate analysis, thoracic LN involvement emerged as the only independent factor (hazard ratio 4.86, 95 % confidence interval 1.56-15.14, p = 0.006). CONCLUSIONS: PM offers a chance for long-term survival in selected patients with CRC and previously resected liver metastasis. Thoracic LN involvement predicted poor prognosis; therefore, significant efforts should be undertaken for adequate staging of the mediastinum before PM. In addition, adequate intraoperative LN sampling allows proper prognostic stratification and enrollment in novel adjuvant therapy trials.