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OBJECTIVES: This case series aimed to determine the feasibility of simultaneous modified Ravitch and David procedures for Marfan syndrome patients with pectus excavatum and annuloaortic ectasia. METHODS: Between March 2014 and December 2019, 7 consecutive patients underwent simultaneous surgery of modified Ravitch and David procedures for pectus excavatum and annuloaortic ectasia. The completion of cardiac surgery and sternal closure were followed by the modified Ravitch procedure. The bilateral fourth to seventh costal cartilages were resected, the sternal body partially wedge resected and the sternum raised anteriorly with re-suture. An oblique incision was performed on bilateral third costal cartilages, and they were fixed on top of each other, with the medial end superior and the lateral end inferior. The sternum was raised anteriorly, bypassing the fourth to seventh rib ends through the back of the sternum with threads. The feasibility and safety of the procedure were assessed through a retrospective review of the patients' clinical charts. RESULTS: The total sample had a median age of 28 years and comprised 5 males and 2 females. There was a significant difference in the preoperative and postoperative median Haller index, which were 6.8 and 3.9, respectively. All patients were discharged without serious complications, and there was no significant recurrence of pectus excavatum at 35-92 months postoperatively. CONCLUSIONS: The results of our case series suggest the feasibility of one-stage surgery for pectus excavatum combined with cardiac surgery using the modified Ravitch procedure. Future efforts should be tailored for more uneventful postoperative clinical courses.
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BACKGROUND: Thrombotic microangiopathy is a syndrome characterized by microangiopathic hemolytic anemia and platelet aggregation, which is caused by endothelial injury, microcirculation thrombosis, and fibrin deposition. Transplant-associated thrombotic microangiopathy rarely occurs after lung transplantation and the onset is generally later than that after bone marrow or other solid organ transplantation. The treatment is to stop administration of the causal agent, which is often a calcineurin inhibitor, such as tacrolimus and cyclosporine. We herein report the case of a patient with early post-transplant thrombotic microangiopathy after lung transplantation treated by introducing basiliximab and temporarily stopping any calcineurin inhibitors until resuming treatment with an alternative calcineurin inhibitor. CASE PRESENTATION: A 58-year-old Asian woman underwent bilateral lung transplantation for hypersensitivity pneumonitis caused by an avian antigen, or bird fancier's lung disease. Postoperatively, she was started on triple immunosuppressive therapy, which included tacrolimus, mycophenolate mofetil, and steroids. On postoperative day 6, she developed thrombocytopenia followed by fever, hemolytic anemia, renal dysfunction, and purpura on her limbs and abdomen. She was diagnosed with transplant-associated thrombotic microangiopathy, and tacrolimus was thought to be the causal agent. We stopped tacrolimus and administered basiliximab. Then, she developed oliguria and needed continuous hemodiafiltration. On postoperative day 14, the platelet count recovered and she was switched from basiliximab to cyclosporine. Using this protocol, worsening thrombotic microangiopathy and acute rejection were avoided. CONCLUSIONS: We report the case of a patient with early post-transplant thrombotic microangiopathy after lung transplantation that was treated with basiliximab. Switching from calcineurin inhibitors using basiliximab may be an option for treating thrombotic microangiopathy without increasing the risk of acute rejection.
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We analyzed an EGFR-mutated lung cancer with a pathologic diagnosis of combined large cell neuroendocrine carcinoma with mixed adenocarcinoma subtypes. Targeted next-generation sequencing of each component suggested that mutations in RB1, TP53, and SMAD4 and apparent loss of heterozygosity of TP53 and SMAD4 accompanied the transition of different adenocarcinoma subtypes. Additional gene mutations including PTEN, MST1R, and PIK3CA were noted during transdifferentiation from acinar adenocarcinoma to large cell neuroendocrine carcinoma. Combined DNA and RNA analysis using Todai OncoPanel revealed that transdifferentiation to different pathologic subtypes occurred in a single tumor through the accumulation of gene mutations.
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OBJECTIVES: Physical biomarkers to stratify patients with lung cancer into subtypes predictive of outcome beyond tumor-related characteristics are underexplored. This study was designed to investigate the clinical utility of preoperative sarcopenia based on respiratory strength and pectoralis muscle mass to predict the risk of death. METHODS: This retrospective study included 346 consecutive patients undergoing curative-intent resection of non-small cell lung cancer from 2009 to 2013. Respiratory strength and muscle mass were assessed by peak expiratory flow rate and pectoralis muscle index (pectoralis muscle area/body mass index) using preoperative spirometry and chest axial images, respectively. Sarcopenia cutoff points were defined by gender-specific medians of peak expiratory flow rates and pectoralis muscle indices. Survival was compared between patients with sarcopenia and patients without. RESULTS: Sarcopenia was present in 98 patients (28.3%) and was significantly associated with advancing age (P < .001). Patients with sarcopenia exhibited worse 5-year overall survival compared with patients without sarcopenia (69.9% vs 87.2%, P < .001). Multivariate analysis revealed that sarcopenia was an independent adverse prognostic factor (hazard ratio, 1.88; 95% confidence interval, 1.09-3.24; P = .023) after adjustment for gender, age, smoking status, coronary heart disease, diffusing capacity for carbon monoxide, neutrophil-to-lymphocyte ratio, albumin, histologic type, and pathologic stage. CONCLUSIONS: Preoperative sarcopenia as identified by the criteria of low respiratory strength and reduced pectoralis muscle mass is significantly associated with poor overall survival. This may help to develop more individualized management strategies and optimize longitudinal care for patients.
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Carcinoma Pulmonar de Células não Pequenas/cirurgia , Neoplasias Pulmonares/cirurgia , Força Muscular , Músculos Peitorais/diagnóstico por imagem , Pneumonectomia , Respiração , Sarcopenia/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/fisiopatologia , Feminino , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/fisiopatologia , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão , Pico do Fluxo Expiratório , Músculos Peitorais/fisiopatologia , Pneumonectomia/efeitos adversos , Pneumonectomia/mortalidade , Valor Preditivo dos Testes , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Sarcopenia/mortalidade , Sarcopenia/fisiopatologia , Fatores de Tempo , Resultado do TratamentoRESUMO
The use of bioartificial lungs may represent a breakthrough for the treatment of end-stage lung disease. The present study aimed to evaluate the feasibility of transplanting bioengineered lungs created from autologous cells. Porcine decellularized lung scaffolds were seeded with porcine recipient-derived airway and vascular cells. The porcine recipient-derived cells were collected from lung tissue obtained by pulmonary wedge resection. Following culture of autologous cells in the scaffolds, the resulting grafts were unilaterally transplanted into porcine recipients (nâ¯=â¯3). Allograft left unilateral lung transplantation was performed in the control group (nâ¯=â¯3). Left unilateral transplantation of decellularized grafts was also performed in a separate control group (nâ¯=â¯2). In vivo functions were assessed for 2 hours after transplantation. Histologic evaluation and immunostaining showed the presence of airway and vascular cells in the bioengineered lungs. No animals survived in the decellularized transplant group, whereas all animals survived in the bioengineered transplant and allotransplant groups. However, bioengineered lung grafts showed marked bullous changes. The oxygen exchange was comparable between the bioengineered lung graft transplant and allograft transplant groups. However, the carbon dioxide gas exchange of the bioengineered lung graft transplant group was significantly lower than that of the allograft transplant group at 2 hours after transplantation (4.10 ± 0.87 mm Hg vs 24.7 ± 10.1 mm Hg, Pâ¯=â¯0.02). Transplantation of bioartificial lung grafts created from autologous cells was feasible in the super-acute phase. However, bullous changes and poor carbon dioxide gas exchange remain limitations of this method.
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Transplante de Pulmão , Pulmão , Animais , Modelos Animais de Doenças , Pulmão/cirurgia , Transplante de Pulmão/efeitos adversos , Oxigênio , SuínosRESUMO
Lung transplantation (LTx) and lung volume reduction surgery are established therapies for end-stage chronic obstructive pulmonary disease. Although native lung hyperinflation is a well-known complication of unilateral LTx for chronic obstructive pulmonary disease, the unilateral procedure continues to be performed because of severe shortages of cadaveric donors. As native lung hyperinflation can adversely affect the graft, all possible protection should be provided for patients with one-lobe transplantation. We report an emphysematous juvenile patient who successfully underwent simultaneous living-donor, single-lobe LTx and volume reduction in the contralateral lung.
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Enfisema , Transplante de Pulmão , Doença Pulmonar Obstrutiva Crônica , Enfisema Pulmonar , Enfisema/cirurgia , Humanos , Pulmão , Pneumonectomia , Enfisema Pulmonar/cirurgiaRESUMO
BACKGROUND: Not all non-small cell lung cancer (NSCLC) patients possess drug-targetable driver mutations, and response rates to immune checkpoint blockade therapies also remain unsatisfactory. Therefore, more effective treatments are still needed. Here, we report the results of a phase 2 clinical trial of adoptive cell therapy using zoledronate-expanded autologous Vγ9Vδ2 T-cells for treatment-refractory NSCLC. METHODS: NSCLC patients who had undergone at least two regimens of standard chemotherapy for unresectable disease or had had at least one treatment including chemotherapy or radiation for recurrent disease after surgery were enrolled in this open-label, single-arm, multicenter, phase 2 study. After preliminary testing of Vγ9Vδ2 T-cell proliferation, autologous peripheral blood mononuclear cells were cultured with zoledronate and IL-2 to expand the Vγ9Vδ2 T-cells. Cultured cells (>1×109) were intravenously administered every 2 weeks for six injections. The primary endpoint of this study was progression-free survival (PFS), and secondary endpoints included overall survival (OS), best objective response rate (ORR), disease control rate (DCR), safety and immunomonitoring. Clinical efficacy was defined as median PFS significantly >4 months. RESULTS: Twenty-five patients (20 adenocarcinoma, 4 squamous cell carcinoma and 1 large cell carcinoma) were enrolled. Autologous Vγ9Vδ2 T-cell therapy was administered to all 25 patients, of which 16 completed the foreseen course of 6 injections of cultured cells. Median PFS was 95.0 days (95% CI 73.0 to 132.0 days); median OS was 418.0 days (179.0-479.0 days), and best overall responses were 1 partial response, 16 stable disease (SD) and 8 progressive disease. ORR and DCR were 4.0% (0.1%-20.4%) and 68.0% (46.5%-85.1%), respectively. Severe adverse events developed in nine patients, mostly associated with disease progression. In one patient, pneumonitis and inflammatory responses resulted from Vγ9Vδ2 T-cell infusions, together with the disappearance of a massive tumor. CONCLUSIONS: Although autologous Vγ9Vδ2 T-cell therapy was well tolerated and may have an acceptable DCR, this trial did not meet its primary efficacy endpoint. TRIAL REGISTRATION NUMBER: UMIN000006128.
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Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Receptores de Antígenos de Linfócitos T gama-delta/metabolismo , Ácido Zoledrônico/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ácido Zoledrônico/farmacologiaRESUMO
BACKGROUND: Preoperative lung surface localization is effective in sublobar resection for small lung nodules. However, the efficacy may vary depending on the underlying conditions of the lung and tumor, as well as the technique. This study aimed to evaluate the efficacy and limitations of preoperative lung surface localization for wedge resection by analyzing the outcomes of computed tomography (CT)-guided percutaneous marking and virtual-assisted lung mapping (VAL-MAP). METHODS: We investigated 215 patients who underwent curative wedge resection for malignant tumors using CT-guided localization or VAL-MAP from 1998 to 2018 in our institute. Each resected nodule was assessed for successful resection, which was defined as complete resection with adequate margins. RESULTS: One-hundred-and-nineteen patients with 153 nodules were included. The overall successful resection rate was 87.6%. The successful resection rate was significantly lower for nodules with intraoperative adhesion than those without intraoperative adhesion (75.0% vs. 90.1%; P=0.034), and for tumors requiring deep resection margins (>31 mm) than those requiring shallow margins (≤31 mm) (76.7% vs. 94.6%; P=0.002). Although the successful resection rate for nodules resected using CT-guided localization was significantly lower in cases with versus without intraoperative adhesion (54.5% vs. 86.7%; P=0.048), the successful resection rate for nodules resected using VAL-MAP was not influenced by the presence or absence of adhesion (85.7% vs. 93.4%; P=0.491). CONCLUSIONS: A requirement for deeper resection and the presence of intraoperative adhesion were limitations of preoperative lung surface localization for curative pulmonary wedge resection.
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OBJECTIVES: The impact of sarcopenia on the outcome in patients following resection of non-small cell lung cancer is yet to be fully determined. This study aimed to evaluate the clinical utility of a computed tomography-based pectoralis muscle assessment, which reflects sarcopenia, to predict the risk of postoperative outcomes. MATERIALS AND METHODS: This retrospective study included 347 consecutive patients undergoing curative-intent resection of non-small cell lung cancer from 2009 to 2013. The pectoralis muscle index (pectoralis muscle area/body mass index) was assessed at the level of the fourth thoracic vertebra on chest axial images. The primary outcomes were compared between the lowest gender-specific quintile (sarcopenia) and the other quintiles according to the index. The prognostic significance of low pectoralis muscle index was calculated by the Cox proportional hazards regression model. A propensity score matching analysis was performed to adjust the differences in clinical characteristics. RESULTS: Sixty-nine patients were identified with sarcopenia according to the lowest gender-specific quintile of pectoralis muscle index. Patients with sarcopenia exhibited worse 5-year overall survival rate compared with patients without sarcopenia (64.2â¯% vs. 86.7â¯%, P < 0.001). Even in stage I non-small cell lung cancer, the rate of 5-year overall survival in the sarcopenia group was lower than that in the non-sarcopenia group (74.2â¯% vs. 92.4â¯%, P = 0.001). Multivariate analysis revealed that low pectoralis muscle index was independently associated with adverse overall survival (hazard ratio: 2.09, 95â¯% confidence interval: 1.20-3.62, P = 0.009). After propensity score matching, the prognostic impact of sarcopenia based on low pectoralis muscle index was also robust for overall survival (hazard ratio: 3.23, 95â¯% confidence interval: 1.38-7.60, P = 0.007). CONCLUSIONS: Low pectoralis muscle index was significantly associated with poor long-term outcomes in patients with localized non-small cell lung cancer after curative surgery. This may help assist preoperative risk stratification and longitudinal management after surgery.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Sarcopenia , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Músculo Esquelético/patologia , Músculos Peitorais/cirurgia , Prognóstico , Estudos Retrospectivos , Sarcopenia/diagnóstico , Tomografia Computadorizada por Raios XRESUMO
OBJECTIVE: ɤ-glutamyltranspeptidase is an enzyme expressed in various malignancies including lung cancer. It rapidly activates non-fluorescent ɤ-glutamyl hydroxymethyl rhodamine green to highly fluorescent hydroxymethyl rhodamine green. The resultant tumor fluorescence is therefore an indicator of cellular ɤ-glutamyltranspeptidase activity. We have explored the use of ɤ-glutamyl hydroxymethyl rhodamine green as an intraoperative imaging tool for visualizing cancers. Herein, we evaluated the potential of the tumor fluorescence as a postoperative prognostic indicator. METHODS: We included patients with non-small cell lung cancer who had undergone radical resection from 2012 to 2014 in the study. We assessed the fluorescence intensity of the resected tumor and normal lung tissue by ex vivo imaging using ɤ-glutamyl hydroxymethyl rhodamine green. RESULTS: Sixty-seven patients were eligible for the study (adenocarcinomas, n = 44; squamous cell carcinoma, n = 14; other histologies, n = 8). The pathological stages were I, II, III, and IV in 39, 15, 12, and 1 patient, respectively. Based on the fluorescence of the tumor tissue, the patients were divided into high fluorescence (n = 33) and low fluorescence (n = 34) groups. The 5-year overall survival rate was significantly higher in the high fluorescence group (72.7%) compared to the low fluorescence group (47.1%, P = 0.025). Similarly, pathological stage I patients of the high fluorescence group had higher 5-year overall survival (85.7% vs. 44.4%, P = 0.009) and recurrence-free survival (76.2% vs. 44.4% P = 0.044) rates compared to those of the low fluorescence group. CONCLUSIONS: ɤ-glutamyl hydroxymethyl rhodamine green fluorescence is a good postoperative prognostic indicator in patients with non-small cell lung cancer.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Fluorescência , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/cirurgia , Prognóstico , RodaminasRESUMO
An 80-year-old man with a history of cutaneous squamous cell carcinoma (SCC) was referred to our department for a solitary lung nodule. The nodule was surgically resected and diagnosed as SCC. Because the lung lesion and a previous skin lesion showed similar histological findings, the origin of the lung tumor was uncertain. Next-generation sequencing using a targeted driver oncogene panel was applied for the further examination. The lung lesion was diagnosed as primary lung SCC, as the two tumors possessed distinct somatic mutations in TP53. Recent advances in clinical sequencing have enabled us to obtain an accurate diagnosis in pathologically challenging cases.
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Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/patologia , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/patologia , Idoso de 80 Anos ou mais , Diagnóstico Diferencial , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Mutação , Proteína Supressora de Tumor p53/genéticaRESUMO
We report a case of giant solitary fibrous tumor( SFT) of the pleura postoperatively complicated with probable reexpansion pulmonary edema and atrial fibrillation. An 85-year-old woman was diagnosed to have a 13 cm sized intrathoracic neoplasm. Upon thoracotomy, the tumor was found to pedunculate from the right lung with no direct invasion to the surrounding structures. Complete resection of the tumor and expansion of the right lung was obtained. Histopathology revealed the tumor was a benign SFT arising from the visceral pleura. An infiltrative shadow in the right lower lung field soon after the surgery suggested a reexpansion pulmonary edema, which eventually recovered within a week. The patient suffered from a refractory atrial fibrillation that led to a congestive heart failure requiring an intensive medical treatment. It is emphasized that thoracic surgeons should be aware of these postoperative complications in treating such a case like this.
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Fibrilação Atrial , Neoplasias Pleurais , Edema Pulmonar , Tumor Fibroso Solitário Pleural , Idoso de 80 Anos ou mais , Feminino , Humanos , Pleura , Tumor Fibroso Solitário Pleural/cirurgia , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: Patients with lung cancer with a history of treatment often undergo curative surgical resection. However, the impact of previous cancer treatment on the outcome of lung cancer remains unclear. METHODS: We conducted a retrospective study of patients who underwent curative resection for non-small cell lung cancer between 1998 and 2011. We collected clinicopathologic data and patients were divided into groups by previous history of cancer treatment. Comparisons between groups, estimation of survival rates, and multivariate analyses were performed. Propensity score matching was used to create cohorts with reduced bias. RESULTS: Of 878 patients, 196 (22.3%) had previous extrathoracic malignancies, and stage I lung cancer was more frequent in this group (P < .001). In multivariate analysis of the whole cohort, older patients, men, non-adenocarcinoma histologic type, more advanced pathologic stage of lung cancer, interstitial pneumonia, and previous extrathoracic malignancies were associated with appreciably worse prognosis. When propensity score matched cohorts were compared, prognosis was significantly worse in patients with previous extrathoracic malignancies than patients without (5-year survival rates, 75.3% vs 82.7%; P = .009), although recurrence was not frequently seen (5-year recurrence-free rates, 78.7% vs 83.0%; P = .491). CONCLUSIONS: Because treatment history of extrathoracic malignancy was not associated with postsurgical lung cancer recurrence, proposing curative resection could be justifiable if the previous cancer is deemed cured or controlled. However, the results showing that patients with previous cancer history have a worse survival rate than patients without should be taken into account when curative surgery is considered.
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Carcinoma Pulmonar de Células não Pequenas/mortalidade , Neoplasias Pulmonares/mortalidade , Segunda Neoplasia Primária/mortalidade , Idoso , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estadiamento de Neoplasias , Segunda Neoplasia Primária/cirurgia , Prognóstico , Pontuação de Propensão , Estudos Retrospectivos , Fatores de Risco , Taxa de SobrevidaRESUMO
INTRODUCTION: The prognostic implications of having patients with idiopathic pleuroparenchymal fibroelastosis (IPPFE) on lung transplantation waiting lists have been unclear. In Japan, where a severe shortage of brain-dead donors remains a major limitation for organ transplantation, it is particularly important to predict the prognoses of patients when they are listed for transplantation. The purpose of this study was to investigate the characteristics of lung transplantation candidates with IPPFE and the influence of those characteristics on prognosis. METHODS: This was a retrospective review of 29 consecutive adult lung transplant candidates with idiopathic interstitial pneumonia between January 2014 and April 2018. RESULTS: Eight patients with IPPFE and 21 with other types of idiopathic interstitial pneumonia were included. Body mass index (median 17.1 kg/m2 vs 23.5 kg/m2, P < .01) and ratio of anteroposterior to transverse diameter of the thoracic cage were significantly lower (0.530 vs 0.583, P = .02) in the IPPFE group. Patients with a body mass index <20.0 kg/m2 (P = .02), 6-minute walk distance <250.0 m (P < .01), ratio of PaO2 to fraction of inspiratory oxygen <300.0 mm Hg (P < .01), and an inability to perform the diffusing capacity of carbon monoxide test (P < .01) had significantly shorter survival times in the other idiopathic interstitial pneumonia, but not in the IPPFE, group. Some patients with IPPFE survived for long enough to undergo transplantation. CONCLUSIONS: Patients with IPPFE waiting for transplantation have some distinctive characteristics and should be retained on waiting lists to receive transplants.
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Pneumonias Intersticiais Idiopáticas/patologia , Transplante de Pulmão , Seleção de Pacientes , Listas de Espera , Adulto , Feminino , Humanos , Fibrose Pulmonar Idiopática/patologia , Japão , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos RetrospectivosRESUMO
Next-generation sequencing (NGS) has been implemented in clinical oncology to analyze multiple genes and to guide therapy. In patients with advanced lung cancer, small biopsies such as computed tomography-guided needle biopsy (CTNB), endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) and transbronchial biopsy (TBB) are less invasive and are preferable to resection to make a pathological diagnosis. However, the quality of DNA/RNA and NGS from small lung tumor biopsy samples is unknown. Between April 2017 and March 2018, 107 consecutive samples were obtained from thoracic tumors or metastatic sites for targeted NGS analysis. Fifteen samples were obtained through CTNB, 11 through EBUS-TBNA, 11 through TBB and 70 through surgical resection. All samples were formalin-fixed and paraffin-embedded. DNA and RNA quality was measured using the ddCq method and the percentage of RNA fragments above 200 nucleotides (DV200), respectively. Our custommade probes were designed to capture exon sequences of 464 cancer-related genes and transcripts of 463 genes. DNA and RNA yield from the 3 biopsy methods were similar, and less than the yield obtained from resected samples. The quality of DNA and RNA was similar across all methods. Overall, 12 of 15 CTNB samples (80%), all 11 EBUS-TBNA samples, and 9 of 11 TBB samples (82%) underwent successful NGS assays from DNA. NGS analysis from RNA was successful in all 12 CTNB samples, 9 of 11 EBUS-TBNA samples (82%), and 8 of 11 TBB samples (73%). CTNB, EBUS-TBNA and TBB mostly resulted in adequate DNA and RNA quality and enabled high-quality targeted NGS analysis.
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Neoplasias Pulmonares/genética , Biópsia/métodos , DNA/genética , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , RNA/genéticaRESUMO
OBJECTIVES: Spread through air space (STAS) is recognized as a pattern of invasion in lung adenocarcinoma and has been reported to be a predictor of recurrence and survival in patients with early-stage lung adenocarcinoma. However, this parameter has not been studied well in stage III (N2) lung adenocarcinoma. In this study, we evaluated the association between STAS invasion patterns and recurrence and survival in stage III (N2) lung adenocarcinoma. METHODS: We retrospectively reviewed data from 76 patients at University of Tokyo with stage III (N2) lung adenocarcinoma who underwent surgery from August 1998 to December 2013. Statistical analysis was performed to determine the impact of STAS invasion clinicopathological features and clarify the relationship between this pattern of invasion and survival. RESULTS: Tumour STAS was observed in 46 of 76 patients (60.5%) and was significantly associated with the presence of lymphatic invasion (P < 0.001), papillary components (P < 0.001) and micropapillary components (P < 0.001). STAS was also significantly associated with recurrence (5-year recurrence-free probability: 19.0% vs 46.1%, P < 0.05). Univariate analyses showed that STAS was a significant risk factor for recurrence (hazard ratio 1.94, 95% confidence interval 1.07-3.51; P = 0.029). CONCLUSIONS: The presence of STAS invasion pattern is a significant risk factor for recurrence in stage III (N2) lung adenocarcinoma.
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Adenocarcinoma de Pulmão/patologia , Neoplasias Pulmonares/patologia , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Adenocarcinoma de Pulmão/mortalidade , Adenocarcinoma de Pulmão/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Japão/epidemiologia , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Recidiva Local de Neoplasia/mortalidade , Pneumonectomia , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida/tendênciasRESUMO
OBJECTIVE: Conventional virtual-assisted lung mapping (VAL-MAP), also termed multi-spot preoperative bronchoscopic lung marking, necessitates post-mapping computed tomography (CT) to confirm the locations of dye markings. We hypothesized that electromagnetic navigation bronchoscopy (ENB) simplifies VAL-MAP by omitting post-mapping CT. METHODS: Under general anesthesia, real-time navigation bronchoscopy was conducted using ENB to reach a site as close to the planned location as possible, and indigo carmine was injected. Initially, surgery was then performed (no-adjustment group; 5 lesions of 3 patients). Later, on-site adjustment was added before surgery (adjustment group; 4 lesions of 4 patients), in which the locational information of ENB was transferred to a radiology workstation to construct an adjusted three-dimensional image. The accuracy of each predicted marking location was graded based on intraoperative observation. After the analysis, 19 patients with 21 lesions underwent ENB VAL-MAP with on-site adjustment (practice set) to evaluate the surgical outcomes. RESULTS: The accuracy of the predicted marking location was significantly higher in the adjustment than no-adjustment group (4.7 ± 0.7 vs. 3.4 ± 1.2, respectively; P = 0.01), especially among the markings for which the bronchoscope did not reach the planned location (4.5 ± 0.8 vs. 2.6 ± 0.5, respectively; P = 0.004). In the practice set, the lung map quality was satisfactory and the resection outcome was successful with a sufficient macroscopic resection margin in 19/21 lesions (90.5%). CONCLUSION: The ENB VAL-MAP quality was improved by adding on-site adjustment, achieving clinical outcomes similar to conventional VAL-MAP. The logistic challenge of post-mapping CT in conventional VAL-MAP can be partially overcome by ENB VAL-MAP with on-site adjustment.
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Broncoscopia/métodos , Neoplasias Pulmonares/cirurgia , Pneumonectomia/métodos , Cirurgia Assistida por Computador/métodos , Idoso , Fenômenos Eletromagnéticos , Feminino , Humanos , Imageamento Tridimensional , Masculino , Pessoa de Meia-Idade , Cuidados Pré-Operatórios , Reprodutibilidade dos Testes , Tomografia Computadorizada por Raios XRESUMO
PURPOSE: To better determine suitable resection lines for sublobar lung resection, especially to obtain sufficient resection depth, a novel technique of virtual-assisted lung mapping (VAL-MAP) 2.0 was developed by combining multispot dye marks (conventional VAL-MAP) and a deeply placed microcoil. DESCRIPTION: With the patient under local anesthesia and sedation, multiple dye marks were bronchoscopically made on the lung surface. Microcoils were then bronchoscopically placed centrally to the tumor to indicate deep resection margins. Postmapping computed tomography confirmed the marking locations. EVALUATION: Six patients underwent VAL-MAP 2.0: 5 for wedge resection and 1 for segmentectomy. The mean diameter and depth of the targeted lesions were 10.0 ± 4.1 and 12.6 ± 10.3 mm, respectively. In total, 18 dye marks and 9 microcoils were placed without major complications. The microcoils were successfully identified with intraoperative fluoroscopy, effectively assisting the surgeons' decision regarding the deep resection lines. CONCLUSIONS: This study confirmed the safety and feasibility of VAL-MAP 2.0. This technique effectively assisted surgeons to obtain sufficient resection margins in sublobar lung resection, even when removing deeply located lesions.
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Broncoscopia , Neoplasias Pulmonares/cirurgia , Pneumonectomia/métodos , Corantes , Fluoroscopia , Humanos , Imageamento Tridimensional , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Margens de Excisão , Nódulo Pulmonar Solitário/diagnóstico por imagem , Cirurgia Assistida por ComputadorRESUMO
BACKGROUND: Patients with thymomas are at high risk of developing extrathymic malignancies. We investigated the impact of extrathymic malignancies on the prognosis of patients with thymoma who underwent surgery and the risk factors for postoperative extrathymic malignancies. METHODS: A multicenter retrospective review of 252 patients who underwent surgical resection of thymomas from January 1977 to March 2016 was conducted. The exclusion criteria were recurrent thymoma, rare types of thymoma, and missing data. The overall number and incidence of extrathymic malignancies were calculated. Potential predictors of extrathymic malignancies were also evaluated. RESULTS: Two hundred twenty-eight patients were analyzed. Fifty-five extrathymic malignancies were observed (23 postoperative, 8 synchronous, and 24 preoperative). Among the overall cohort, the incidence of extrathymic malignancies significantly increased the patients' risk of death (hazard ratio [HR], 4.02; 95% confidence interval [CI], 1.72 to 9.40; p < 0.01). Among patients aged less than 70 years, the incidence of extrathymic malignancies was an independent risk factor for death. The incidence of postoperative extrathymic malignancies was significantly higher in patients with indolent forms of thymoma (type A/AB/B1) than aggressive forms (type B2/B3) (p = 0.02). In the multivariate analysis, indolent forms of thymoma (type A/AB/B1) (HR, 4.03; 95% CI, 1.12 to 14.6, p = 0.03) and a history of ever having smoked (HR, 5.29; 95% CI, 1.30 to 21.6; p = 0.02) were significant risk factors for the cumulative incidence of postoperative extrathymic malignancies. CONCLUSIONS: Extrathymic malignancies increased the risk of death in patients with thymomas. Indolent forms of thymoma and a history of ever having smoked were risk factors for postoperative extrathymic malignancies.