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OBJECTIVE: The purpose of this study was to assess performance in the Brazilian Lung Cancer Registry Database by using the parsimonious EuroLung risk models for morbidity and mortality. METHODS: The EuroLung1 and EuroLung2 models were tested and evaluated through calibration (calibration plot, Brier score, and the Hosmer-Lemeshow test) and discrimination (ROC AUCs), in a national multicenter registry of 1,031 patients undergoing anatomic lung resection. RESULTS: The evaluation of performance in Brazilian health care facilities utilizing risk-adjustment models, specifically EuroLung1 and EuroLung2, revealed substantial miscalibration, as evidenced by calibration plots and Hosmer-Lemeshow tests in both models. In terms of calibration, EuroLung1 exhibited a calibration plot with overlapping points, characterized by a slope of 1.11 and a Brier score of 0.15; the Hosmer-Lemeshow test yielded a statistically significant p-value of 0.015; and the corresponding ROC AUC was 0.678 (95% CI: 0.636-0.721). The EuroLung2 model displayed better calibration, featuring fewer overlapping points in the calibration plot, with a slope of 1.22, with acceptable discrimination, as indicated by a ROC AUC of 0.756 (95% CI: 0.670-0.842). Both models failed to accurately predict morbidity and mortality outcomes in this specific health care context. CONCLUSIONS: Discrepancies between the EuroLung model predictions and outcomes in Brazil underscore the need for model refinement and for a probe into inefficiencies in the Brazilian health care system.

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ABSTRACT Objective: The purpose of this study was to assess performance in the Brazilian Lung Cancer Registry Database by using the parsimonious EuroLung risk models for morbidity and mortality. Methods: The EuroLung1 and EuroLung2 models were tested and evaluated through calibration (calibration plot, Brier score, and the Hosmer-Lemeshow test) and discrimination (ROC AUCs), in a national multicenter registry of 1,031 patients undergoing anatomic lung resection. Results: The evaluation of performance in Brazilian health care facilities utilizing risk-adjustment models, specifically EuroLung1 and EuroLung2, revealed substantial miscalibration, as evidenced by calibration plots and Hosmer-Lemeshow tests in both models. In terms of calibration, EuroLung1 exhibited a calibration plot with overlapping points, characterized by a slope of 1.11 and a Brier score of 0.15; the Hosmer-Lemeshow test yielded a statistically significant p-value of 0.015; and the corresponding ROC AUC was 0.678 (95% CI: 0.636-0.721). The EuroLung2 model displayed better calibration, featuring fewer overlapping points in the calibration plot, with a slope of 1.22, with acceptable discrimination, as indicated by a ROC AUC of 0.756 (95% CI: 0.670-0.842). Both models failed to accurately predict morbidity and mortality outcomes in this specific health care context. Conclusions: Discrepancies between the EuroLung model predictions and outcomes in Brazil underscore the need for model refinement and for a probe into inefficiencies in the Brazilian health care system.

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PURPOSE: This paper aims to present the results of a series of several Brazilian institutions that have been carrying out lung cancer screening (LCS). MATERIALS AND METHODS: This is a retrospective, cohort study, with follow-up of individuals of both sexes, with a heavy smoking history, who participated in LCS programs between December 2013 and January 2021 in six Brazilian institutions located in the states of São Paulo, Rio Grande do Sul, and Bahia. RESULTS: Three thousand four hundred seventy individuals were included, of which 59.8% were male (n = 2,074) and 50.6% were current smokers (n = 1,758), with 60.7 years (standard deviation 8.8 years). Lung-RADS 4 was observed in 233 (6.7%) patients. Biopsy was indicated by minimally invasive methods in 122 patients (3.5%). Two patients who demonstrated false-negative biopsies and lung cancer were diagnosed in follow-up. Diagnosis of lung cancer was observed in 74 patients (prevalence rate of 2.1%), with 52 (70.3%) in stage I or II. Granulomatous disease was found in 20 patients. There were no statistical differences in the incidence of lung cancer, biopsies, granulomatous disease, and Lung-RADS 4 nodules between public and private patients. CONCLUSION: There are still many challenges and obstacles in the implementation of LCS in developing countries; however, our multi-institutional data were possible to obtain satisfactory results in these scenarios and to achieve similar results to the main international studies. Granulomatous diseases did not increase the number of lung biopsies. The authors hope that it could stimulate the creation of organized screening programs in regions still endemic for tuberculosis and other granulomatous diseases.

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OBJECTIVE: To report the experience of a routine follow-up program based on medical visits and chest CT. METHODS: This was a retrospective study involving patients followed after complete surgical resection of non-small cell lung cancer between April of 2007 and December of 2015. The follow-up program consisted of clinical examination and chest CT. Each follow-up visit was classified as a routine or non-routine consultation, and patients were considered symptomatic or asymptomatic. The outcomes of the follow-up program were no evidence of cancer, recurrence, or second primary lung cancer. RESULTS: The sample comprised 148 patients. The median time of follow-up was 40.1 months, and 74.3% of the patients underwent fewer chest CTs than those recommended in our follow-up program. Recurrence and second primary lung cancer were found in 17.6% and 11.5% of the patients, respectively. Recurrence was diagnosed in a routine medical consultation in 69.2% of the cases, 57.7% of the patients being asymptomatic. Second primary lung cancer was diagnosed in a routine medical appointment in 94.1% of the cases, 88.2% of the patients being asymptomatic. Of the 53 patients who presented with abnormalities on chest CT, 41 (77.3%) were diagnosed with cancer. CONCLUSION: Most of the cases of recurrence, especially those of second primary lung cancer, were confirmed by chest CT in asymptomatic patients, indicating the importance of a strict follow-up program that includes chest CTs after surgical resection of lung cancer.

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Th17/Treg imbalance plays a pivotal role in COPD development and progression. We aimed to assess Th17/Treg-related intracellular signaling at different COPD stages in local and systemic responses. Lung tissue and/or peripheral blood samples were collected and divided into non-obstructed (NOS), COPD stages I and II, and COPD stages III and IV groups. Gene expression of STAT3 and -5, RORγt, Foxp3, interleukin (IL)-6, -17, -10, and TGF-ß was assessed by RT-qPCR. IL-6, -17, -10, and TGF-ß levels were determined by ELISA. We observed increased STAT3, RORγt, Foxp3, IL-6, and TGF-ß gene expression and IL-6 levels in the lungs of COPD I and II patients compared to those of NOS patients. Regarding the systemic response, we observed increased STAT3, RORγt, IL-6, and TGF-ß gene expression in the COPD III and IV group and increased IL-6 levels in the COPD I and II group. STAT5 was increased in COPD III and IV patients, although there was a decrease in Foxp3 expression and IL-10 levels in the COPD I and II and COPD III and IV groups, respectively. We demonstrated that an increase in Th17 intracellular signaling in the lungs precedes this increase in the systemic response, whereas Treg intracellular signaling varies between the compartments analyzed in different COPD stages.

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BACKGROUND: Cancer patients configure a risk group for complications or death by COVID-19. For many of them, postponing or replacing their surgical treatments is not recommended. During this pandemic, surgeons must discuss the risks and benefits of treatment, and patients should sign a specific comprehensive Informed consent (IC). OBJECTIVES: To report an IC and an algorithm developed for oncologic surgery during the COVID-19 outbreak. METHODS: We developed an IC and a process flowchart containing a preoperative symptoms questionnaire and a PCR SARS-CoV-2 test and described all perioperative steps of this program. RESULTS: Patients with negative questionnaires and tests go to surgery, those with positive ones must wait 21 days and undergo a second test before surgery is scheduled. The IC focused both on risks and benefits inherent each surgery and on the risks of perioperative SARS-CoV-2 infections or related complications. Also, the IC discusses the possibility of sudden replacement of medical staff member(s) due to the pandemic; the possibility of unexpected complications demanding emergency procedures that cannot be specifically discussed in advance is addressed. CONCLUSIONS: During the pandemic, specific tools must be developed to ensure safe experiences for surgical patients and prevent them from having misunderstandings concerning their care.

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BACKGROUND: There are limited data on surgical complications for patients that have delayed surgery after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We aimed to analyze the surgical outcomes of patients submitted to surgery after recovery from SARS-CoV-2 infection. METHODS: Asymptomatic patients that had surgery delayed after preoperative reverse-transcription polymerase chain reaction (RT-PCR) for SARS-CoV-2 were matched in a 1:2 ratio for age, type of surgery and American Society of Anesthesiologists to patients with negative RT-PCR for SARS-CoV-2. RESULTS: About 1253 patients underwent surgical procedures and were subjected to screening for SARS-CoV-2. Forty-nine cases with a delayed surgery were included in the coronavirus disease (COVID) recovery (COVID-rec) group and were matched to 98 patients included in the COVID negative (COVID-neg) group. Overall, 22 (15%) patients had 30-days postoperative complications, but there was no statistically difference between groups -16.3% for COVID-rec and 14.3% for COVID-neg, respectively (odds ratio [OR] 1.17:95% confidence interval [CI] 0.45-3.0; p = .74). Moreover, we did not find difference regarding grades more than or equal to 3 complication rates - 8.2% for COVID-rec and 6.1% for COVID-neg (OR 1.36:95%CI 0.36-5.0; p = .64). There were no pulmonary complications or SARS-CoV-2 related infection and no deaths within the 30-days after surgery. CONCLUSIONS: Our study suggests that patients with delayed elective surgeries due to asymptomatic preoperative positive SARS-CoV-2 test are not at higher risk of postoperative complications.

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ABSTRACT Objective: To report the experience of a routine follow-up program based on medical visits and chest CT. Methods: This was a retrospective study involving patients followed after complete surgical resection of non-small cell lung cancer between April of 2007 and December of 2015. The follow-up program consisted of clinical examination and chest CT. Each follow-up visit was classified as a routine or non-routine consultation, and patients were considered symptomatic or asymptomatic. The outcomes of the follow-up program were no evidence of cancer, recurrence, or second primary lung cancer. Results: The sample comprised 148 patients. The median time of follow-up was 40.1 months, and 74.3% of the patients underwent fewer chest CTs than those recommended in our follow-up program. Recurrence and second primary lung cancer were found in 17.6% and 11.5% of the patients, respectively. Recurrence was diagnosed in a routine medical consultation in 69.2% of the cases, 57.7% of the patients being asymptomatic. Second primary lung cancer was diagnosed in a routine medical appointment in 94.1% of the cases, 88.2% of the patients being asymptomatic. Of the 53 patients who presented with abnormalities on chest CT, 41 (77.3%) were diagnosed with cancer. Conclusion: Most of the cases of recurrence, especially those of second primary lung cancer, were confirmed by chest CT in asymptomatic patients, indicating the importance of a strict follow-up program that includes chest CTs after surgical resection of lung cancer.

RESUMO Objetivo: Relatar a experiência de um programa de acompanhamento de rotina baseado em consultas médicas e TC de tórax. Métodos: Estudo retrospectivo envolvendo pacientes acompanhados após ressecção cirúrgica completa de câncer de pulmão de células não pequenas entre abril de 2007 e dezembro de 2015. O programa de acompanhamento consistiu em exame clínico e TC de tórax. Cada visita de acompanhamento foi classificada como uma consulta de rotina ou fora da rotina, e os pacientes foram considerados sintomáticos ou assintomáticos. Os desfechos do programa de acompanhamento foram ausência de evidência de câncer, recidiva ou segundo câncer de pulmão primário. Resultados: A amostra foi composta por 148 pacientes. A mediana do tempo de acompanhamento foi de 40,1 meses, e 74,3% dos pacientes realizaram menos TCs do que as recomendadas em nosso programa de acompanhamento. Recidiva e segundo câncer de pulmão primário foram encontrados em 17,6% e 11,5% dos pacientes, respectivamente. A recidiva foi diagnosticada em uma consulta médica de rotina em 69,2% dos casos, sendo 57,7% dos pacientes assintomáticos. O segundo câncer de pulmão primário foi diagnosticado em consulta médica de rotina em 94,1% dos casos, sendo 88,2% dos pacientes assintomáticos. Dos 53 pacientes que apresentaram anormalidades na TC de tórax, 41 (77,3%) foram diagnosticados com câncer. Conclusões: A maioria dos casos de recidiva, principalmente os de segundo câncer de pulmão primário, foi confirmada por TC de tórax em pacientes assintomáticos, indicando a importância de um programa de acompanhamento rigoroso que inclua TC de tórax após ressecção cirúrgica de câncer de pulmão.

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INTRODUCTION: Technological advancements in computed tomography (CT) have enabled the frequent detection of small pulmonary nodules (PNs), especially in patients with an oncologic history. It is important the malignant versus benign etiology of PNs be determined. The aim of the present study was to evaluate the behavior and clinical/radiological characteristics of subcentimeter PNs detected by CT in oncologic patients. METHODS: An observational, longitudinal, retrospective and single-center study was conducted with a sample of 100 patients with a diagnosis of a primary malignant solid tumor outside of the lungs who developed indeterminate subcentimeter PNs (n = 251) detected on consecutive thoracic CT scans from 2015 to 2017. Follow-up CTs for each patients were examined in each of three periods (0-3 months, 3-6 months, and 6 months to 1 year). RESULTS: In our study sample, 28 patients (28 %) showed one or more signs suspicious of pulmonary metastasis, including ≥50 % PN growth, nodule growth followed by size reduction in patients undergoing chemotherapy, and the appearance of multiple nodules. The majority (56 %) of the PNs were detected during the 3-6-month follow-up CT scan. PNs with irregular, lobuled, or spiculated margins exhibited faster growth than PNs with regular, smooth margins. Malignancy of PNs was found to be significantly associated with being male, a primary colorectal cancer diagnosis, and advanced stage disease. CONCLUSION: Our findings reinforce the necessity of an individualized CT follow-up strategy for patients with an oncologic history, as well as the importance of early nodule screening, with the inter-scan interval being dependent on the primary neoplasm.

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OBJECTIVE: To analyze determinants of prognosis in patients with bronchial carcinoid tumors treated surgically and the potential concomitance of such tumors with second primary neoplasms. METHODS: This was a retrospective analysis of 51 bronchial carcinoid tumors treated surgically between 2007 and 2016. Disease-free survival (DFS) was calculated by the Kaplan-Meier method, and determinants of prognosis were evaluated. Primary neoplasms that were concomitant with the bronchial carcinoid tumors were identified by reviewing patient charts. RESULTS: The median age was 51.2 years, 58.8% of the patients were female, and 52.9% were asymptomatic. The most common histology was typical carcinoid (in 80.4%). Five-year DFS was 89.8%. Ki-67 expression was determined in 27 patients, and five-year DFS was better among the patients in whom Ki-67 expression was ≤ 5% than among those in whom it was > 5% (100% vs. 47.6%; p = 0.01). Concomitant primary neoplasms were observed in 14 (27.4%) of the 51 cases. Among the concomitant primary neoplasms that were malignant, the most common was lung adenocarcinoma, which was observed in 3 cases. Concomitant primary neoplasms were more common in patients who were asymptomatic and in those with small tumors. CONCLUSIONS: Surgical resection is the mainstay treatment of bronchopulmonary carcinoid tumors and confers a good prognosis. Bronchial carcinoid tumors are likely to be accompanied by second primary neoplasms.

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ABSTRACT Objective: To analyze determinants of prognosis in patients with bronchial carcinoid tumors treated surgically and the potential concomitance of such tumors with second primary neoplasms. Methods: This was a retrospective analysis of 51 bronchial carcinoid tumors treated surgically between 2007 and 2016. Disease-free survival (DFS) was calculated by the Kaplan-Meier method, and determinants of prognosis were evaluated. Primary neoplasms that were concomitant with the bronchial carcinoid tumors were identified by reviewing patient charts. Results: The median age was 51.2 years, 58.8% of the patients were female, and 52.9% were asymptomatic. The most common histology was typical carcinoid (in 80.4%). Five-year DFS was 89.8%. Ki-67 expression was determined in 27 patients, and five-year DFS was better among the patients in whom Ki-67 expression was ≤ 5% than among those in whom it was > 5% (100% vs. 47.6%; p = 0.01). Concomitant primary neoplasms were observed in 14 (27.4%) of the 51 cases. Among the concomitant primary neoplasms that were malignant, the most common was lung adenocarcinoma, which was observed in 3 cases. Concomitant primary neoplasms were more common in patients who were asymptomatic and in those with small tumors. Conclusions: Surgical resection is the mainstay treatment of bronchopulmonary carcinoid tumors and confers a good prognosis. Bronchial carcinoid tumors are likely to be accompanied by second primary neoplasms.

RESUMO Objetivo: Analisar os determinantes do prognóstico em pacientes com tumores carcinoides brônquicos tratados cirurgicamente e possível segunda neoplasia primária concomitante. Métodos: Trata-se de uma análise retrospectiva de 51 tumores carcinoides brônquicos tratados cirurgicamente entre 2007 e 2016. A sobrevida livre de doença (SLD) foi calculada pelo método de Kaplan-Meier, e os determinantes do prognóstico foram avaliados. As neoplasias primárias concomitantes aos tumores carcinoides brônquicos foram identificadas por meio da análise dos prontuários dos pacientes. Resultados: A mediana de idade foi de 51,2 anos, 58,8% dos pacientes eram do sexo feminino e 52,9% eram assintomáticos. A classificação histológica mais comum foi carcinoide típico (em 80,4%). A SLD em cinco anos foi de 89,8%. A expressão de Ki-67 foi determinada em 27 pacientes, e a SLD em cinco anos foi melhor nos pacientes nos quais a expressão de Ki-67 foi ≤ 5% do que naqueles nos quais a expressão de Ki-67 foi > 5% (100% vs. 47,6%; p = 0,01). Neoplasias primárias concomitantes foram observadas em 14 (27,4%) dos 51 casos. Entre as neoplasias primárias malignas concomitantes, a mais comum foi o adenocarcinoma pulmonar, observado em 3 casos. Neoplasias primárias concomitantes foram mais comuns em pacientes assintomáticos e naqueles com tumores pequenos. Conclusões: A resseção cirúrgica é o principal tratamento de tumores carcinoides broncopulmonares e propicia um bom prognóstico. É provável que tumores carcinoides brônquicos se relacionem com segunda neoplasia primária.

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Herein, we aimed at identifying global transcriptome microRNA (miRNA) changes and miRNA target genes in lung adenocarcinoma. Samples were selected as training (N = 24) and independent validation (N = 34) sets. Tissues were microdissected to obtain >90% tumor or normal lung cells, subjected to miRNA transcriptome sequencing and TaqMan quantitative PCR validation. We further integrated our data with published miRNA and mRNA expression datasets across 1,491 lung adenocarcinoma and 455 normal lung samples. We identified known and novel, significantly over- and under-expressed (p ≤ 0.01 and FDR≤0.1) miRNAs in lung adenocarcinoma compared to normal lung tissue: let-7a, miR-10a, miR-15b, miR-23b, miR-26a, miR-26b, miR-29a, miR-30e, miR-99a, miR-146b, miR-181b, miR-181c, miR-421, miR-181a, miR-574 and miR-1247. Validated miRNAs included let-7a-2, let-7a-3, miR-15b, miR-21, miR-155 and miR-200b; higher levels of miR-21 expression were associated with lower patient survival (p = 0.042). We identified a regulatory network including miR-15b and miR-155, and transcription factors with prognostic value in lung cancer. Our findings may contribute to the development of treatment strategies in lung adenocarcinoma.

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OBJECTIVES: To evaluate the preliminary results obtained using diffusion-weighted magnetic resonance imaging and the apparent diffusion coefficient for planning computed tomography-guided biopsies of selected mediastinal lesions. METHODS: Eight patients with mediastinal lesions suspicious for malignancy were referred for computed tomography-guided biopsy. Diffusion-weighted magnetic resonance imaging and apparent diffusion coefficient measurement were performed to assist in biopsy planning with diffusion/computed tomography fused images. We selected mediastinal lesions that could provide discordant diagnoses depending on the biopsy site, including large heterogeneous masses, lesions associated with lung atelectasis or consolidation, lesions involving large mediastinal vessels and lesions for which the results of biopsy using other methods and histopathological examination were divergent from the clinical and radiological suspicion. RESULTS: In all cases, the biopsy needle was successfully directed to areas of higher signal intensity on diffusion-weighted sequences and the lowest apparent diffusion coefficient within the lesion (mean, 0.8 [range, 0.6-1.1]×10-3 mm2/s), suggesting high cellularity. All biopsies provided adequate material for specific histopathological diagnoses of four lymphomas, two sarcomas and two thymomas. CONCLUSION: Functional imaging tools, such as diffusion-weighted imaging and the apparent diffusion coefficient, are promising for implementation in noninvasive and imaging-guided procedures. However, additional studies are needed to confirm that mediastinal biopsy can be improved with these techniques.

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OBJECTIVES: To evaluate the preliminary results obtained using diffusion-weighted magnetic resonance imaging and the apparent diffusion coefficient for planning computed tomography-guided biopsies of selected mediastinal lesions. METHODS: Eight patients with mediastinal lesions suspicious for malignancy were referred for computed tomography-guided biopsy. Diffusion-weighted magnetic resonance imaging and apparent diffusion coefficient measurement were performed to assist in biopsy planning with diffusion/computed tomography fused images. We selected mediastinal lesions that could provide discordant diagnoses depending on the biopsy site, including large heterogeneous masses, lesions associated with lung atelectasis or consolidation, lesions involving large mediastinal vessels and lesions for which the results of biopsy using other methods and histopathological examination were divergent from the clinical and radiological suspicion. RESULTS: In all cases, the biopsy needle was successfully directed to areas of higher signal intensity on diffusion-weighted sequences and the lowest apparent diffusion coefficient within the lesion (mean, 0.8 [range, 0.6-1.1]×10-3 mm2/s), suggesting high cellularity. All biopsies provided adequate material for specific histopathological diagnoses of four lymphomas, two sarcomas and two thymomas. CONCLUSION: Functional imaging tools, such as diffusion-weighted imaging and the apparent diffusion coefficient, are promising for implementation in noninvasive and imaging-guided procedures. However, additional studies are needed to confirm that mediastinal biopsy can be improved with these techniques. .

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BACKGROUND: The purpose of this study was to evaluate the usefulness of diffusion-weighted magnetic resonance imaging (DW-MRI) and positron emission tomography/computed tomography (PET/CT) in planning transthoracic CT-guided biopsies of lung lesions. METHODS: Thirteen patients with lung lesions suspicious for malignancy underwent CT-guided biopsy. Chest DW-MRI and apparent diffusion coefficient (ADC) calculation were performed to aid biopsy planning with fused images. MRI was indicated due to large heterogeneous masses, association with lung atelectasis/consolidation/necrosis, and/or divergent results of other biopsy type and histopathology versus clinical/radiological suspicion. Eight patients underwent PET/CT to identify appropriate areas for biopsy. RESULTS: Mean patient (n = 9 males) age was 59 (range, 30 to 78) years. Based on DW-MRI results, biopsies targeted the most suspicious areas within lesions. All biopsied areas showed higher DW signal intensity and lower ADCs (mean, 0.79 (range, 0.54 to 1.2) × 10(-3) mm2/s), suggesting high cellularity. In patients who underwent PET/CT, areas with higher 18-fluorodeoxyglucose concentrations (standard uptake value mean, 7.7 (range, 3.6 to 13.7)) corresponded to areas of higher DW signal intensity and lower ADCs. All biopsies yielded adequate material for histopathological diagnosis. CONCLUSIONS: Functional imaging is useful for lung biopsy planning. DW-MRI and PET/CT increase overall performance and enable the collection of adequate material for specific diagnosis.

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