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1.
Artigo em Inglês | MEDLINE | ID: mdl-31919516

RESUMO

OBJECTIVES: No significant data are available to assess whether complex sleeve lobectomy (complex-SL) can be considered comparable to conventional lobectomy (CL) in terms of surgical outcome. The purpose of this study was to compare surgical and oncological outcomes of complex-SL with CL in patients with lung cancer. METHODS: Between 2000 and 2015, a total of 568 patients who underwent open CL (defined as resection of only 1 lobe) and 187 patients who underwent SL were analysed. The SL group was divided into 2 subgroups: standard-SL (bronchial SL, n = 106) and complex-SL (n = 81) (defined as bronchial sleeve resection together with another surgical intervention: bronchovascular SL, n = 40; vascular SL, n = 26; atypical bronchoplasty with resection of more than 1 lobe, n = 12; bronchial SL + chest wall resection, n = 3). RESULTS: The complex-SL group had more patients with chronic obstructive pulmonary disease (COPD) (25.9% vs 12.5%, P = 0.001), neoadjuvant treatment (39.5% vs 12.0%, P < 0.001), advanced-stage non-small-cell lung cancer (53.2% vs 33.1%, P = 0.001) and low preoperative forced expiratory volume in 1 s (77.2% vs 84.3%, P = 0.004) than the CL group. The overall surgical mortality (in-hospital or 30-day) was 2.6% (n = 20); it was 2.8% for CL and 2.8% for complex-SL. Postoperative complications occurred in 34.9% of the CL group and 39.5% of the complex-SL group (P = 0.413). The pulmonary complication rate was similar between the groups (24.1% for CL, 27.2% for complex-SL, P = 0.552). The 5-year survival in the CL group was 57.1%, and in the complex-SL group it was 56.2% (P = 0.888). Multivariate analysis showed that TNM stage (P < 0.001) and N status (P < 0.001) were significant and independent negative prognostic factors for survival. CONCLUSIONS: Complex-SL had a comparable outcome to CL, although the complex-SL group had more patients with advanced-stage NSCLC, low preoperative forced expiratory volume in 1 s and COPD.

2.
Front Immunol ; 10: 2236, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31681257

RESUMO

Background: Chronic granulomatous disease (CGD) is caused by a malfunctioning nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex in phagocytes, leading to impaired bacterial and fungal killing and hyperinflammation. Objective: To characterize macrophage subsets and cytokine/chemokine signaling loops involved in CGD tissue hyperinflammation. Methods: Cytokine/chemokine production and surface marker expression were analyzed in inflamed tissue of four CGD patients and compared to cytokine/chemokine released by CGD macrophages upon priming to different macrophage subpopulations. Furthermore, the re-priming capacity of CGD pro-inflammatory M1 to M2a anti-inflammatory macrophages was evaluated. Results: In human CGD inflammatory tissue, IL-18 and IFN-γ were detected in significant quantity. Immunofluorescence analysis identified macrophages as one source of IL-18 in inflamed tissue. In vitro, CGD macrophages could be primed and re-primed into all inflammatory/anti-inflammatory macrophage subpopulations. IL-18 was also released by M1 CGD and control macrophages. Conclusion: CGD pro-inflammatory M1 macrophages remain M1 primed in vivo. As CGD M1 macrophages can be re-primed to anti-inflammatory M2a phenotype in vitro, macrophages are kept in M1 state in vivo by a persistent pro-inflammatory environment. Our results suggest a paracrine signaling loop between M1 macrophage derived IL-18 and non-macrophage derived IFN-γ maintaining macrophage pro-inflammatory activity in CGD tissue.

3.
Swiss Med Wkly ; 149: w20064, 2019 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-30994925

RESUMO

AIM OF THE STUDY: Non-intubated, video-assisted thoracoscopic surgery (NiVATS) has been successfully developed in several centres worldwide. Local anaesthesia techniques and techniques to perform thoracoscopic surgery on a spontaneously breathing lung are the two key elements which must be adopted to establish a NiVATS programme. We established NiVATS by performing bilateral, uniportal sympathectomies, and compared it to classical video-assisted thoracoscopic surgery (VATS) under general anaesthesia with double-lumen intubation. METHODS: Ten consecutive bilateral VATS sympathectomies were compared with ten consecutive NiVATS procedures. Nineteen of the procedures were for palmar hyperhidrosis and one was for facial blushing. Duration of anaesthesia, surgery and hospitalisation, perioperative complications, side effects and quality of life before and after sympathectomy were analysed. RESULTS: Median age was 26.5 years (range 17–55) and mean BMI in the NiVATS group was 21.8 (range 19.1–26.3). NiVATS sympathectomies were performed as outpatient procedures significantly more often (9/10 vs 3/10, p = 0.008). Quality of life was significantly increased after sympathectomy in all patients, with no significant differences between the NiVATS and the VATS groups. There were no differences between the two groups regarding compensatory sweating (40 vs 50%, p = 0.66). The duration of anaesthesia, not including the time required for the surgery, was significantly shorter in the NiVATS group (p <0.001). The duration of surgery, from the first local anaesthesia until the last skin suture, was significantly longer in the NiVATS group (p = 0.04), but showed a constant decline during the learning curve, from 95 minutes initially to 48 minutes for the last procedure. Costs were significantly lower in the NiVATS group (p = 0.04). CONCLUSION: Thoracoscopic sympathectomy is a suitable procedure with which to establish a NiVATS programme. Patients are usually young and of healthy weight, facilitating the learning curve for the local anaesthesia techniques and the surgery. Compared to VATS, sympathectomy is more likely to be performed as an outpatient procedure and has a lower cost, while safety and efficacy are maintained.

4.
J Thorac Dis ; 10(Suppl 23): S2704-S2710, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30210822

RESUMO

Background: Radiotherapy is recommended as primary local therapy for inoperable patients with non-small cell lung cancer (NSCLC). We hypothesized that selected patients with advanced emphysema could be candidates for surgery and improved functional outcome might result in addition to low mortality and morbidity and successful cancer control when sublobar resection in a lung volume reduction surgery (LVRS) concept is applied. Methods: All patients with NSCLC and severe emphysema who underwent cancer resection in a LVRS concept between 2003 and 2015 were included for analysis. Postoperative 90-day mortality, complications, survival and lung function with forced expiratory volume in one second pre-operatively and three months postoperatively served as endpoints. Results: Fourteen patients were included. Three procedures were bilateral and eleven unilateral, eight have been performed with thoracoscopy and six with conversion to an open procedure due to adhesions. In ten patients, tumor resection was atypical and in four patients an anatomic segmentectomy was performed. All patients had lung volume reduction. Prolonged air leak occurred in three patients. Perioperative 90-mortality was zero. Median pre-operative forced expiratory volume in one second was 32.5% and increased to 37% (P=0.002) 3 months following surgery. Three and 5-year survival rates were 50% and 35%, respectively. Conclusions: Sublobar resection of NSCLC combined with LVRS in patients with severely impaired lung function due to emphysema can be performed with low mortality and morbidity making it an alternative treatment modality to radiotherapy. This approach allows cancer resection in marginal patients and improves emphysema symptoms simultaneously.

5.
Ann Thorac Cardiovasc Surg ; 24(6): 296-302, 2018 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-29962390

RESUMO

PURPOSE: Utilization of donation after circulatory death (DCD) donors has the potential to decrease donor shortage in lung transplantation (LTx). This study reviews the long-term outcome of LTx from DCD donors. METHODS: We included all consecutive DCD (Maastricht Category III) and all donations after brain death (DBD) donor lung transplants at our Center performed between January 2012 and February 2017. Data were analyzed comparing the two groups in regard of survival after LTx as primary outcome. RESULTS: Median withdrawal to cardiac arrest time was 17 min (interquartile range [IQR]: 11.5-20.5). Median cardiac arrest to cold perfusion was 32 min (IQR: 24.5-36.5). Primary graft dysfunction (PGD) grade 3 at T72 occurred in three recipients. Chronic lung allograft dysfunction (CLAD) led to death in two cases. In DCD group, there was no 90-day mortality. In DCD, group 1- and 3-year survival rates were 100% and 80%. In DBD group, 1- and 3-year survival rates were 85% and 69% (p = 0.4). CONCLUSIONS: Our report confirmed the comparable outcome from DCD donors compared with DBD donors. Utility of DCD donors is a safe option to overcome donor shortage.


Assuntos
Morte Encefálica , Seleção do Doador , Transplante de Pulmão/métodos , Doadores de Tecidos/provisão & distribução , Adulto , Feminino , Sobrevivência de Enxerto , Humanos , Transplante de Pulmão/efeitos adversos , Transplante de Pulmão/mortalidade , Masculino , Pessoa de Meia-Idade , Países Baixos , Complicações Pós-Operatórias/etiologia , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
6.
J Thorac Dis ; 10(3): E175-E178, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29707367

RESUMO

We present an exemplary case of an immunocompromised patient with pulmonary mucormycosis successfully treated by a combination of surgical removal of the mucor and urokinase to control the recurring hemothorax. The use of urokinase in hemothoraces is a way to reduce repetitive surgeries in weak patients.

7.
Pathol Res Pract ; 214(4): 572-578, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29580750

RESUMO

Oncogenic rearrangements leading to targetable gene fusions are well-established cancer driver events in lung adenocarcinoma. Accurate and reliable detection of these gene fusions is crucial to select the appropriate targeted therapy for each patient. We compared the targeted next-generation-sequencing Oncomine Focus Assay (OFA; Thermo Fisher Scientific) with conventional ALK FISH and anti-Alk immunohistochemistry in a cohort of 52 lung adenocarcinomas (10 ALK rearranged, 18 non-ALK rearranged, and 24 untested cases). We found a sensitivity and specificity of 100% for detection of ALK rearrangements using the OFA panel. In addition, targeted next generation sequencing allowed us to analyze a set of 23 driver genes in a single assay. Besides EML4-ALK (11/52 cases), we detected EZR-ROS1 (1/52 cases), KIF5B-RET (1/52 cases) and MET-MET (4/52 cases) fusions. All EML4-ALK, EZR-ROS1 and KIF5B-RET fusions were confirmed by multiplexed targeted next generation sequencing assay (Oncomine Solid Tumor Fusion Transcript Kit, Thermo Fisher Scientific). All cases with EML4-ALK rearrangement were confirmed by Alk immunohistochemistry and all but one by ALK FISH. In our experience, targeted next-generation sequencing is a reliable and timesaving tool for multiplexed detection of targetable rearrangements. Therefore, targeted next-generation sequencing represents an efficient alternative to time-consuming single target assays currently used in molecular pathology.


Assuntos
Adenocarcinoma/genética , Proteínas de Ciclo Celular/genética , Rearranjo Gênico , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Neoplasias Pulmonares/genética , Proteínas Associadas aos Microtúbulos/genética , Receptores Proteína Tirosina Quinases/genética , Serina Endopeptidases/genética , Adenocarcinoma/diagnóstico , Adenocarcinoma/patologia , Adenocarcinoma de Pulmão , Quinase do Linfoma Anaplásico , Estudos de Coortes , Fusão Gênica , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/patologia , Patologia Molecular , Estudos Retrospectivos , Sensibilidade e Especificidade , Análise de Sequência de RNA
8.
Anal Biochem ; 547: 77-83, 2018 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-29408474

RESUMO

The use of optimal cutting temperature (OCT) medium has served to improve the long-term preservation of surgical tissue specimens. Unfortunately, the presence of polymers in OCT has been found to generate signal interference in proteomic-based techniques. Indeed the presence of OCT medium in tissue lysates precludes the analysis of activity based proteomic profiles obtained from lung adenocarcinoma (LuAdCa) resection specimens. In order to probe this question further tissue lysates were prepared from 47 lung non-neoplastic and tumour, node, metastasis (TNM) stage 1 LuAdCa resection specimens embedded with or without OCT, and data of activity based multiplex profiles of protein tyrosine kinase peptide substrates were obtained. We found that changes in overall phosphorylation level coincided with the use of OCT and subsequently developed an OCT per peptide median correcting strategy by performing median centering on the values of each peptide. Application of this post-analytical strategy not only can identify changes in kinase activity but can also assist in identifying novel targets for therapeutic intervention against LuAdCa.


Assuntos
Adenocarcinoma de Pulmão/metabolismo , Neoplasias Pulmonares/metabolismo , Proteínas de Neoplasias/metabolismo , Proteínas Tirosina Quinases/metabolismo , Proteômica/métodos , Adenocarcinoma de Pulmão/patologia , Feminino , Humanos , Neoplasias Pulmonares/patologia , Masculino , Fosforilação
9.
Eur J Cardiothorac Surg ; 53(3): 596-602, 2018 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-28957998

RESUMO

OBJECTIVES: Lung volume reduction surgery (LVRS) and lung transplantation (LTx) are the treatments of choice in selected patients with end-stage emphysema. Recently, the history of LVRS has been questioned due to reduced post-transplant survival. We aim to address this question by reviewing our experience, which is the largest single-centre series of LVRS followed by LTx. METHODS: We reviewed our prospectively recorded database in patients with emphysema undergoing LTx between 1993 and 2014. Preoperative workup and postoperative outcomes were compared according to previous LVRS status. The Kaplan-Meier test was used for survival analysis and compared with a log-rank test. RESULTS: One hundred and seventeen patients (66 men; mean age 56 ± 7 years) underwent LTx during the study period, 52 of whom had previous LVRS (LVRS + LTx). The mean time from LVRS to LTx was 45 ± 31 months. Patients were slightly older and had extensive smoking history in the LVRS + LTx group. Overall, in-hospital mortality was 10%, which did not differ significantly regardless of the history of LVRS (P = 0.8). The median survival for the LTx-only and LVRS + LTx groups was 86 [95% confidence interval (CI) 56-116] and 107 (95% CI 77-137) months, respectively (P = 0.6). CONCLUSIONS: Previous LVRS does not negatively affect short-term and long-term outcomes following LTx in patients with end-stage emphysema. The history of LVRS should not preclude the candidacy for LTx. Considering the limited number of donors available, the LVRS option should be kept in mind for the postponement of LTx in carefully selected patients.


Assuntos
Transplante de Pulmão/mortalidade , Transplante de Pulmão/estatística & dados numéricos , Pulmão/cirurgia , Pneumonectomia/estatística & dados numéricos , Enfisema/cirurgia , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
10.
Oncotarget ; 8(40): 68599-68613, 2017 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-28978141

RESUMO

Despite constant improvement in existing therapeutic efforts, the overall survival rate of lung cancer patients remains low. Enzyme activities may identify new therapeutically targetable biomarkers and overcome the marked lack of correlation between cellular abundance of translated proteins and corresponding mRNA expression levels. We analysed tyrosine kinase activities to classify lung adenocarcinoma (LuAdCa) resection specimens based on their underlying changes in cellular processes and pathways that are agents of or result from malignant transformation. We characterised 71 same-patient pairs of early-stage LuAdCa and non-neoplastic LuAdCa resection specimen lysates in the presence or absence of a tyrosine kinase inhibitor. We performed ex vivo multiplex tyrosine phosphorylation assays using 144 selected microarrayed kinase substrates. The obtained 76 selected phosphotyrosine signature peptides were subsequently analysed in terms of follow-up treatments and outcomes recorded in the patient files. For tumour, node, metastasis (TNM) stage 1 LuAdCa patients, we noticed a larger tyrosine kinase inhibitor-induced decrease in tyrosine phosphorylation for long-term as opposed to short-term disease survivors, for which 26 of 76 selected peptides were significantly (p < 0.01, FDR < 3%) more inhibited in the long-term survivors. Using statistical class prediction analysis, we obtained a 'prognostic-signature' for long- versus short-term disease survivors and correctly predicted the survival status of 73% of our patients. Our translational approach may assist clinical disease management after surgical resection and may help to direct patients for an optimal treatment strategy.

11.
J Surg Res ; 218: 341-347, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28985871

RESUMO

BACKGROUND: We have shown the beneficial effects of N-acetylcysteine (NAC) on posttransplant lung function, when both donor and recipient were pretreated intravenously. However, systemic treatment of multiorgan donors may not be clinically relevant. Thus, we hypothesized that ex vivo treatment of donors with nebulized NAC would be adequate to prevent from ischemia-reperfusion injury after lung transplantation. METHODS: Lungs were retrieved from domestic pigs and stored at 4°C for 24 h followed by 2 h of ex vivo lung perfusion (EVLP) to administer 50 mg/kg of NAC via nebulization in the NAC group (n = 6). The control group received nebulized saline (n = 5). Left lungs were transplanted and isolated at 1 h of reperfusion by occluding the right main bronchus and pulmonary artery, followed by 5 h of observation. Physiological data during EVLP and after reperfusion were recorded. Inflammatory response, markers of oxidative stress, and microscopic lung injury were analyzed. RESULTS: There was a trend toward better oxygenation throughout reperfusion period in the treatment group, which was accompanied by inhibited inflammatory response related to reduction in myeloperoxidase activity during EVLP and nuclear factor-κB activation at the end of reperfusion. CONCLUSIONS: Ex vivo treatment of donor lungs with inhaled NAC reduced inflammatory response via its antioxidant activity in experimental porcine lung transplantation.


Assuntos
Acetilcisteína/administração & dosagem , Depuradores de Radicais Livres/administração & dosagem , Transplante de Pulmão , Disfunção Primária do Enxerto/prevenção & controle , Animais , Avaliação Pré-Clínica de Medicamentos , Feminino , Suínos
12.
J Nucl Med ; 58(12): 1925-1930, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-28490471

RESUMO

The purpose of this study was to assess various volume-based PET quantification metrics, including metabolic tumor volume and total lesion glycolysis (TLG) with different thresholds, as well as background activity-based PET metrics (background-subtracted lesion activity [BSL] and background-subtracted volume) as prognostic markers for progression-free and overall survival (PFS and OS, respectively) in early-stage I and II non-small cell lung cancer (NSCLC) after resection. Methods: Patients (n = 133) underwent an adequate 18F-FDG PET/CT scan before surgery between January 2003 and December 2010. All PET activity metrics showed a skewed distribution and were log-transformed before calculation of the Pearson correlation coefficients. Survival tree analysis was used to discriminate between high- and low-risk patients and to select the most important prognostic markers. The Akaike information criterion was used to compare 2 univariate models. Results: Within the study time, 36 patients died from NSCLC and 26 patients from other causes. At the end of follow-up, 70 patients were alive, with 67 patients being free of disease. All log-transformed PET metrics showed a strong linear association, with a Pearson correlation coefficient between 0.703 and 0.962. After multiple testing corrections, only 1 prognostic marker contributed a significant split point in the survival tree analysis. Of 10 potential predictors including 7 PET metrics, a BSL greater than 6,852 (P = 0.017) was chosen as split point, assigning 13 patients into a high-risk group. If BSL was removed from the set of predictors, a 42% TLG (TLG42%) of greater than 4,204 (P = 0.023) was chosen as split point. When a dichotomized BSL or TLG42% variable was used for a univariate Cox model, the Akaike information criterion difference of both models was smaller than 2; therefore, the data do not provide evidence that 1 of the 2 prognostic factors is superior. Conclusion: Volume-based PET metrics correlate with PFS and OS and could be used for risk assessment in stage I-II NSCLC. The different PET metrics assessed in this study showed a high correlation; therefore, it is not surprising that there was no significant difference to predict PFS or OS within this study. Overall, patients with large and metabolically active tumors should be considered high risk and might need further treatment after resection. Because all analysis steps were done with the same data, these results should be validated on new patient data.


Assuntos
Neoplasias Brônquicas/diagnóstico por imagem , Neoplasias Brônquicas/cirurgia , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Glicólise , Adenocarcinoma/diagnóstico por imagem , Adenocarcinoma/metabolismo , Adenocarcinoma/cirurgia , Idoso , Idoso de 80 Anos ou mais , Neoplasias Brônquicas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma de Células Escamosas/diagnóstico por imagem , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/cirurgia , Estudos de Coortes , Intervalo Livre de Doença , Feminino , Fluordesoxiglucose F18 , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Valor Preditivo dos Testes , Prognóstico , Compostos Radiofarmacêuticos , Estudos Retrospectivos , Análise de Sobrevida
13.
Interact Cardiovasc Thorac Surg ; 24(5): 740-746, 2017 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-28453802

RESUMO

OBJECTIVES: The objective of this retrospective study was to assess perioperative outcomes, overall survival and freedom from recurrence after induction chemotherapy followed by extrapleural pneumonectomy (EPP) or pleurectomy/decortication (P/D) in patients with mesothelioma in a propensity score matched analysis. METHODS: Between September 1999 and August 2015, 167 patients received multimodality treatment (platinum-based chemotherapy followed by EPP [ n = 141] or P/D [ n = 26]). We performed 2:1 propensity score matching for gender, laterality, epithelioid histological subtype and International Mesothelioma Interest Group (iMig) stage (52 EPP and 26 P/D). RESULTS: Postoperative major morbidity (48% vs 58%, P = 0.5) was similar in both groups; however, the complication profile and severity were different and favoured P/D; the 90-day mortality (8% vs 0%, P = 0.3) rate was lower in P/D although not statistically significant. Prolonged air leak (≥10 days) occurred in 15 patients (58%) undergoing P/D. The intensive care unit stay was significantly longer after EPP ( P = 0.001). Freedom from recurrence was similar for both groups (EPP: median 15 months, 95% confidence interval [CI]: 10-21; P/D: 13 months, 95% CI: 11-17) ( P = 0.2). Overall survival was significantly longer for patients undergoing P/D (median 32 months, 95% CI: 29-35) compared to EPP (23 months, 95% CI: 21-25) ( P = 0.031), but in the P/D group many cases were censored (73%) and the follow-up time was relatively short. CONCLUSIONS: P/D and EPP seem to have similar rates of major morbidity, although the profile of complications is different and more severe after EPP. Freedom from recurrence is comparable in both groups whereas improved overall survival needs to be confirmed in a large patient group with longer follow-up.


Assuntos
Mesotelioma/cirurgia , Pleura/cirurgia , Neoplasias Pleurais/cirurgia , Pneumonectomia/métodos , Complicações Pós-Operatórias/epidemiologia , Pontuação de Propensão , Adulto , Idoso , Feminino , Seguimentos , Humanos , Masculino , Mesotelioma/diagnóstico , Pessoa de Meia-Idade , Morbidade/tendências , Recidiva Local de Neoplasia/epidemiologia , Neoplasias Pleurais/diagnóstico , Estudos Retrospectivos , Taxa de Sobrevida/tendências , Suíça/epidemiologia , Fatores de Tempo , Resultado do Tratamento
14.
J Thorac Dis ; 9(3): E194-E196, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28449502

RESUMO

Bronchial carcinoid tumors (BCTs) represent a subgroup of bronchopulmonary neuroendocrine tumors which have the ability to produce neuropeptides. Merely 2% of BCTs secrete ACTH and less than 1% of patients with Cushing's syndrome (CS) have a BCT. Typical BCTs rarely metastasize. We here present a patient with ectopic CS caused by a typical BCT, which metastasized into a lymph node. This case suggests that the diagnostic work up of CS should be wide and include ectopic ACTH-secreting BCT, and that ACTH secretion can be correlated to a more aggressive type of typical BCTs.

15.
J Thorac Dis ; 9(2): 296-302, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28275477

RESUMO

BACKGROUND: Due to an increased life expectancy in a healthy aging population and a progressive incidence of lung cancer, curative pulmonary resections can be performed even in octogenarians. The present study aims to investigate whether surgery is justified in patients reaching the age of 80 years and older who undergo resection for non-small cell lung cancer (NSCLC). METHODS: In this retrospective multi-centre analysis, the morbidity, mortality and long-term survival of 88 patients (24 females) aged ≥80 who underwent complete resection for lung cancer between 2000 and 2013 were analysed. Only fit patients with few comorbidities, low cardiopulmonary risk, good quality of life and a life expectancy of at least 5 years were included. RESULTS: Curative resections from three thoracic surgery centres included 61 lobectomies, 9 bilobectomies, 6 pneumonectomies and 12 segmentectomies or wide wedge resections with additional systematic mediastinal lymphadenectomy in all cases. Final histology revealed squamous cell carcinoma [33], adenocarcinoma [41], large cell carcinoma [5] or other histological types [9]. Lung cancer stage distribution was 0 [1], I [53], II [17] and IIIA [14]. The overall 90-day mortality was 1.1%. The median hospitalisation and chest drainage times were 10 days (range, 5-27 days) and 5 days (range, 0-17 days), respectively. Thirty-six patients were complication-free (41%). In particular, pulmonary complications occurred in 25 patients (28%). In addition, 23 patients (26%) developed cardiovascular complications requiring medical intervention, while 24 patients (27%) had cerebrovascular complications, urinary tract infection and others. The median survival time was 51 months (range, 1-110 months), and the 5-year overall survival reached 45% without significance between tumour stages. CONCLUSIONS: Curative lung resections in selected octogenarians can be safely performed up to pneumonectomy for all tumour stages with a perioperative mortality, morbidity, and 5-year survival rate comparable to younger cohorts.

16.
Ann Thorac Surg ; 102(5): 1680-1686, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27424471

RESUMO

BACKGROUND: Extracorporeal life support (ECLS) as a bridge to lung retransplantation has been reported only anecdotally. Thus, we analyzed combined data from our center with pooled data from published studies to identify selection criteria for this advanced therapy. METHODS: Four patients at our center were bridged on ECLS to lung retransplantation. Patient data were retrospectively retrieved from electronic records. The MEDLINE database was searched using the PubMed engine and yielded 13 relevant studies that included a minimum of 3 patients bridged to lung retransplantation, and four studies described detailed data on 17 patients. Patient data from our center (n = 4) were pooled with data from the MEDLINE database (n = 17) and analyzed. RESULTS: Of 21 patients, 3 (14%) died on ECLS awaiting retransplantation, and 18 (86%) underwent retransplantation after a median of 37 months (range, 0 to 168 months) after primary transplantation. Type of ECLS was extracorporeal carbon dioxide removal (ECCO2R) in 4, venovenous extracorporeal membrane oxygenation (ECMO) in 7, venoarterial ECMO in 5, or was not mentioned in 2. The 90-day postoperative mortality was 28%. Overall 1-year survival was 48%. Patients bridged to retransplantation with ECCO2R/venovenous ECMO (p = 0.05) or on awake ECMO (p = 0.06) showed strong trends toward better survival in univariate analysis. Univariate and multivariate analysis identified a longer intertransplant interval as a statistically significant favorable prognostic factor. In a selected subgroup of patients (awake ECCO2R/venovenous ECMO support and intertransplant interval >2 years), 1-year survival reached 67%. CONCLUSIONS: Despite limited overall 1-year survival for patients bridged with ECLS to lung retransplantation, careful patient selection may yield an acceptable 1-year survival of 67%.


Assuntos
Oxigenação por Membrana Extracorpórea/métodos , Pneumopatias/cirurgia , Transplante de Pulmão , Humanos , Estudos Multicêntricos como Assunto , Seleção de Pacientes , Reoperação
17.
J Mol Med (Berl) ; 94(6): 725-34, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-26864305

RESUMO

UNLABELLED: Reduced activity of histone deacetylase 2 (HDAC2) has been described in patients with chronic obstructive pulmonary disease (COPD), but the mechanisms resulting in decreased expression of this important epigenetic modifier remain unknown. Here, we employed several in vitro experiments to address the role of microRNAs (miRNAs) on the regulation of HDAC2 in endothelial cells. Manipulation of miRNA levels in human pulmonary artery endothelial cells (HPAEC) was achieved by using electroporation with anti-miRNAs and miRNA mimics. Target prediction software identified miR-223 as a potential repressor of HDAC2. In subsequent stimulation experiments using inflammatory cytokines known to be increased in patients with COPD, miR-223 was found to be significantly induced. Functional analysis demonstrated that overexpression of miR-223 decreased HDAC2 expression and activity in HPAEC. Conversely, HDAC2 expression and activity was preserved in anti-miR-223-treated cells. Direct miRNA-target interaction was confirmed by reporter gene assay. In a next step, reduced expression of HDAC2 was found to increase the levels of the chemokine fractalkine (CX3CL1). In vivo studies confirmed elevated expression levels of miR-223 in mice exposed to cigarette smoke and in emphysematous lung tissue from LPS-treated mice. Moreover, a significant inverse correlation of miR-223 and HDAC2 expression was found in two independent cohorts of COPD patients. These data emphasize that miR-223, the most prevalent miRNA in COPD, controls expression and activity of HDAC2 in pulmonary cells, which, in turn, might alter the expression profile of chemokines. This pathway provides a novel pathogenic link between dysregulated miRNA expression and epigenetic activity in COPD. KEY MESSAGES: Histone deacetylase 2 is directly targeted by miR-223. Levels of miR-223 are induced by interleukin-1ß and tumor necrosis factor-α. miR-223 controls the expression of fractalkine by targeting histone deacetylase 2. miR-223 levels are increased in COPD mouse models. miR-223 levels inversely correlate with HDAC2 expression in COPD patients.


Assuntos
Quimiocina CX3CL1/genética , Histona Desacetilase 2/genética , MicroRNAs/genética , Doença Pulmonar Obstrutiva Crônica/genética , Enfisema Pulmonar/genética , Fumaça/efeitos adversos , Tabaco/toxicidade , Animais , Sequência de Bases , Linhagem Celular , Quimiocina CX3CL1/metabolismo , Misturas Complexas/toxicidade , Modelos Animais de Doenças , Células Endoteliais/citologia , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Epigênese Genética , Histona Desacetilase 2/metabolismo , Humanos , Interleucina-1/farmacologia , Lipopolissacarídeos/farmacologia , Camundongos , MicroRNAs/antagonistas & inibidores , MicroRNAs/metabolismo , Oligorribonucleotídeos Antissenso/genética , Oligorribonucleotídeos Antissenso/metabolismo , Artéria Pulmonar/citologia , Artéria Pulmonar/efeitos dos fármacos , Artéria Pulmonar/metabolismo , Doença Pulmonar Obstrutiva Crônica/metabolismo , Doença Pulmonar Obstrutiva Crônica/patologia , Enfisema Pulmonar/induzido quimicamente , Enfisema Pulmonar/metabolismo , Enfisema Pulmonar/patologia , Transdução de Sinais , Tabaco/química , Fator de Necrose Tumoral alfa/farmacologia
18.
J Nucl Med ; 57(6): 849-54, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-26823566

RESUMO

UNLABELLED: Assessment of tumor response after chemotherapy using (18)F-FDG PET metrics is gaining acceptance. Several studies have suggested that the parameters metabolically active tumor volume (MTV) and total lesion glycolysis (TLG) are superior to SUVmax for measuring tumor burden. However, the measurement of MTV and TLG is still controversial; the most common method uses an absolute threshold of 42% of SUVmax Recently, we implemented a background-adaptive method to determine the background-subtracted lesion activity (BSL) and the background-subtracted volume (BSV). In this study, we investigated the correlation between such PET metrics and histopathologic response in non-small cell lung carcinoma (NSCLC). METHODS: Forty-four NSCLC patients were retrospectively identified. Their PET/CT data on both types of scan before and after neoadjuvant chemotherapy were analyzed regarding SUVmax, MTV, TLG, BSL, and BSV, as well as the relative changes in these parameters. The tumor regression score as an indicator of histopathologic response was scored on hematoxylin- and eosin-stained sections of the surgical specimens using a 4-tiered scale (scores 1-4). The correlation between score and the absolute and relative PET metrics after chemotherapy was analyzed using Spearman rank correlation tests. RESULTS: Tumors that demonstrated a good response after neoadjuvant chemotherapy had significantly lower (18)F-FDG activity than nonresponding tumors (scores 3 and 4: SUVmax, 4.2 [range, 1.8-7.9] vs. scores 1 and 2: SUVmax, 8.1 [range, 1.4-40.4]; P = 0.001). The same was found for change in SUVmax and score (P = 0.001). PET volume metrics based on a 42% fixed threshold for SUVmax did not correlate with score (TLG, P = 0.505; MTV, P = 0.386). However, both of the background activity-based PET volume metrics-BSL and BSV-significantly correlated with score (P < 0.001 each). CONCLUSION: PET volume metrics based on background-adaptive methods correlate better with histopathologic tumor regression score in NSCLC patients under neoadjuvant chemotherapy than algorithms and methods using a fixed threshold (42% SUVmax).


Assuntos
Carcinoma Pulmonar de Células não Pequenas/terapia , Fluordesoxiglucose F18 , Glicólise , Neoplasias Pulmonares/terapia , Terapia Neoadjuvante , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Adulto , Idoso , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Carga Tumoral
19.
Pediatr Pulmonol ; 51(11): 1222-1228, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-26773327

RESUMO

Lung transplantation (LTx) is an accepted therapy in children with end-stage lung diseases. Pediatric-specific experience is considered important in pediatric LTx. We present our institutional experience and its outcome since the year 2000, asking whether different treatment strategies produce comparable outcomes in pediatric lung transplant recipients at our predominantly adult center. This is a retrospective analysis of children and adolescents aged ≤20 years, undergoing LTx between January 2001 and December 2013. Minimum follow-up was 12 months. Primary endpoints were re-transplantation or death. We performed 33 lung transplant procedures in 29 patients. Survival 1 month post-operatively was 96.6%, at 3 months 93.1% and at 12 months 82.8%, respectively. At the end of our follow up, 72.4% of our pediatric cohort was still alive - median post-transplant survival was 59 months (range 0-159). 72.4% of the children were transplanted with support of extracorporeal membrane oxygenation (ECMO), size-reduced donor grafts were used in 69.0%. The differences between post-transplant survival of the "non-ECMO-group" versus the "ECMO-group" (137 vs. 28 months, P=0.7) and "full size" versus "size-reduced bilateral transplants" (61 vs. 28 months, P = 0.7) were not significant, though. There were no anastomotic complications, also not in size-reduced lungs. Our results are well comparable to the international data and show excellent short- and mid-term outcomes. We advocate ECMO-bridge to be considered as a valuable treatment option to prolong time on the waiting list in highly selected patients, as well as size reduction and lobar transplants as a strong strategy to increase the donor pool and reduce donor-recipient size-mismatches. Pediatr Pulmonol. 2016;51:1222-1228. © 2016 Wiley Periodicals, Inc.


Assuntos
Oxigenação por Membrana Extracorpórea , Pneumopatias/cirurgia , Transplante de Pulmão , Adolescente , Criança , Feminino , Humanos , Masculino , Estudos Retrospectivos , Doadores de Tecidos , Resultado do Tratamento , Listas de Espera , Adulto Jovem
20.
Eur J Cardiothorac Surg ; 49(5): 1516-23, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26590183

RESUMO

OBJECTIVES: To analyse the relapse pattern and influence of second-line treatment after recurrence of malignant pleural mesothelioma (MPM) in patients who had previously undergone multimodality treatment. METHODS: Between September 1999 and December 2013, 136 patients underwent macroscopic complete resection (MCR) by extrapleural pneumonectomy after induction chemotherapy for MPM. We analysed 106 patients who presented with recurrent disease until October 2014. Data were retrieved from our mesothelioma database, with additional information regarding precise localization gathered by reviewing the imaging and medical records. RESULTS: The overall recurrence rate was 78% (106/136 patients). The median freedom from recurrence was 9 months after surgery [95% confidence interval (95% CI) 7-10]. Local recurrence only was observed in 33 patients (31%), distant metastases only in 27 patients (26%) and simultaneous distant and local recurrence in 46 patients (43%). Local recurrence was observed significantly less frequently in patients having received adjuvant radiotherapy (19 vs 47%, P = 0.003), but there was no significant impact on overall survival (OS) [radiation: 22 months (95% CI 19-24); no-radiation: 23 months (95% CI 18-27), P = 0.6]. The median OS was 22 months (95% CI 21-24), median post-recurrence survival (PRS) was 7 months (95% CI 5-9) and patients with local recurrence only survived significantly longer (12 months, 95% CI 8-16) compared with patients with distant recurrence only (5 months, 95% CI 2-8) or distant plus local relapse (6 months, 95% CI 3-9; P = 0.04). A total of 78 patients received a second-line therapy after tumour recurrence: chemotherapy (n = 48), local radiotherapy (n = 9), surgery (n = 10) or a combination thereof (n = 11). Patients undergoing second-line treatment survived significantly longer compared with patients not receiving therapy (P < 0.0005). The median PRS after surgery was significantly longer than that of patients receiving chemo-, radio- or chemo-radiotherapy (P = 0.04). CONCLUSIONS: Local recurrence of MPM remains the most frequent type of relapse even after multimodality treatment including MCR. In the present cohort, active treatment seems beneficial to the patient since surgical excision of local tumour relapse has good long-term outcome in selected patients. Thus, second-line treatment may prolong PRS; however, these results need to be confirmed in a prospective manner.


Assuntos
Neoplasias Pulmonares , Mesotelioma , Recidiva Local de Neoplasia , Adulto , Idoso , Terapia Combinada , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/terapia , Masculino , Mesotelioma/epidemiologia , Mesotelioma/mortalidade , Mesotelioma/terapia , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/terapia , Estudos Retrospectivos , Resultado do Tratamento
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