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Hypoxia is a representative tumor characteristic associated with malignant progression in clinical patients. Engineered in vitro models have led to significant advances in cancer research, allowing for the investigation of cells in physiological environments and the study of disease mechanisms and processes with enhanced relevance. In this study, we propose a U-shape pillar strip for a 3D cell-lumped organoid model (3D-COM) to study the effects of hypoxia on lung cancer in a high-throughput manner. We developed a U-pillar strip that facilitates the aggregation of PDCs mixed with an extracellular matrix to make the 3D-COM in 384-plate array form. The response to three hypoxia-activated prodrugs was higher in the 3D-COM than in the 2D culture model. The protein expression of hypoxia-inducible factor 1 alpha (HIF-1α) and HIF-2α, which are markers of hypoxia, was also higher in the 3D-COM than in the 2D culture. The results show that 3D-COM better recapitulated the hypoxic conditions of lung cancer tumors than the 2D culture. Therefore, the U-shape pillar strip for 3D-COM is a good tool to study the effects of hypoxia on lung cancer in a high-throughput manner, which can efficiently develop new drugs targeting hypoxic tumors.
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Ensaios de Triagem em Larga Escala , Neoplasias Pulmonares , Organoides , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/metabolismo , Organoides/metabolismo , Organoides/patologia , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Hipóxia Celular , Técnicas de Cultura de Células em Três Dimensões , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismoRESUMO
OBJECTIVES: To evaluate the prognostic value of TLR from PET/CT in patients with resection margin-negative stage IB and IIA non-small cell lung cancer (NSCLC) and compare high-risk factors necessitating adjuvant treatment (AT). METHODS: Consecutive FDG PET/CT scans performed for the initial staging of NSCLC stage IB and IIA were retrospectively reviewed. The maximum standardized uptake value (SUVmax) of the primary tumor and mean SUV of the liver were acquired. The tumor-to-liver SUV ratio (TLR) was also calculated. Charts were reviewed for basic patient characteristics and high-risk factors for considering AT (poor differentiation, visceral pleura invasion, vascular invasion, tumors > 4 cm, and wedge resection). Statistical analysis was performed using Cox regression analysis and the Kaplan-Meier method. RESULTS: Of the 112 patients included, 15 (13.4%) died, with a median overall survival (OS) of 43.8 months. Twenty-two patients (19.6%) exhibited recurrence, with median disease-free survival (DFS) of 36.0 months. In univariable analysis, pathology, poor differentiation, and TLR were associated with shorter DFS and OS. In multivariable analysis, TLR (hazard ratio [HR] = 1.263, p = 0.008) and differentiation (HR = 3.087, p = 0.012) were associated with shorter DFS. Also, TLR (HR = 1.422, p < 0.001) was associated with shorter OS. CONCLUSION: TLR from FDG PET/CT was an independent prognostic factor for recurrence and survival. PET parameters constitute risk factors for consideration in the decision-making for AT in margin-negative stage IB and IIA NSCLC. CLINICAL RELEVANCE STATEMENT: In this study, TLR from FDG PET/CT was an independent prognostic factor in stage IB-IIA non-small cell cancer patients. Although additional validation studies are warranted, TLR has the potential to be used to determine the need for adjuvant therapy. KEY POINTS: ⢠High TLR is an independent poor prognostic factor in stage IB-IIA NSCLC. ⢠Adjuvant treatment should be considered in patients with high TLR following complete tumor resection.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Hepáticas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/patologia , Prognóstico , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Fluordesoxiglucose F18 , Neoplasias Pulmonares/patologia , Estudos Retrospectivos , Estadiamento de Neoplasias , Neoplasias Hepáticas/patologia , Compostos RadiofarmacêuticosRESUMO
BACKGROUND: Brain metastasis is a rare event in patients with hepatocellular carcinoma (HCC). This retrospective study aimed to identify the prognostic factors and determine the outcomes of patients with brain metastases from HCC. METHODS: About 86 patients with brain metastases (0.6%) from HCC were identified from two institutions; of them, 32 underwent tumor-removing surgery or stereotactic radiosurgery (SRS) with or without adjuvant whole brain radiotherapy (WBRT) (group 1), 30 had WBRT alone (group 2), and 24 received conservative treatment (group 3). Estimates for overall survival (OS) after brain metastases were determined, and clinical prognostic factors were identified. RESULTS: The median OS after development of brain metastases was 50 days. About 75 (87.2%) patients had lung metastases at the time of brain metastasis diagnosis. Group 1 showed better OS, followed by group 2 and group 3, sequentially (p < 0.001). Univariate analyses showed that treatment with curative intent (surgery or SRS), Child-Pugh class A, alpha-fetoprotein level < 400 ng/ml, and recursive partitioning analysis classification I or II were associated with improved survival (p < 0.001, 0.002, 0.029, and 0.012, respectively). Multivariate analysis showed that treatment with curative intent and Child-Pugh class A was associated with improved OS (p < 0.001 and 0.009, respectively). CONCLUSION: Although the overall prognosis of patients with brain metastases from HCC is extremely poor, patients actively treated with surgery or radiosurgery have prolonged survival, suggesting that interventions to control intracranial disease are important in these patients.
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Neoplasias Encefálicas/mortalidade , Carcinoma Hepatocelular/mortalidade , Neoplasias Hepáticas/mortalidade , Radiocirurgia/mortalidade , Adulto , Idoso , Neoplasias Encefálicas/secundário , Neoplasias Encefálicas/cirurgia , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/cirurgia , Feminino , Humanos , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
BACKGROUND AND OBJECTIVE: Standard surgical management for early stage lung cancer is lobectomy with mediastinal lymph node dissection. The feasibility of limited resection remains controversial; we retrospectively assessed lung cancer-specific survival (LCSS) and overall survival (OS) in early stage non-small cell lung cancer (NSCLC) to evaluate whether segmentectomy is comparable to standard lobectomy. METHODS: Patients with primary NSCLC of 20 mm or less who were diagnosed from 2000 to 2014 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. To compare the two surgical interventions, a propensity score analysis was performed between lobectomy and segmentectomy. RESULTS: Of the 15 358 patients analysed, there were 14 549 lobectomies and 809 segmentectomies. The 5-year OS was 76% for the lobectomy group and 74.4% for the segmentectomy group. There were no significant differences in OS or LCSS among patients who underwent lobectomy versus segmentectomy, as demonstrated by the propensity-matched hazard ratio (HR) for OS (HR: 1.195, 95% CI: 0.993-1.439) and LCSS (HR: 1.124, 95% CI: 0.860-1.469). The inverse propensity-weighted analysis also supported these results. Segmentectomy was more likely to be performed in elderly patients. In the subset of patients aged ≥75 years, the segmentectomy group demonstrated comparable OS (HR: 1.17, 95% CI: 0.87-1.58, P = 0.31) and LCSS (HR: 0.94, 95% CI: 0.59-1.51, P = 0.81), compared with the lobectomy group. CONCLUSION: Equivalent OS and LCSS were demonstrated in patients with primary NSCLC of 20 mm or less without lymph node or distant metastasis.
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Carcinoma Pulmonar de Células não Pequenas/cirurgia , Neoplasias Pulmonares/cirurgia , Pneumonectomia/métodos , Idoso , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Pontuação de Propensão , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Programa de SEER , Taxa de Sobrevida , Carga TumoralRESUMO
BACKGROUND: Sublobar resection of lung cancer may benefit patients with lung cancer presenting as ground-glass opacity (GGO) nodules. The purpose of this study was to evaluate the effect of margin width on recurrence after sublobar resection in patients with clinical N0 non-small cell lung cancer presenting as GGO-predominant nodule. METHODS: We conducted a retrospective chart review of 91 patients treated for clinical N0 non-small cell lung cancer ≤3 cm by sublobar resection with clear resection margins. We assigned them to two groups: GGO-predominant tumor and solid-predominant tumor. Each group was subdivided into two groups according to the margin width: resection margin ≤5 mm and resection margin >5 mm. We analyzed the clinicopathological findings and survival among these four groups. RESULTS: There was no recurrence in GGO-predominant tumors after sublobar resection. Margin width did not influence the recurrence in GGO-predominant tumors. In the cases of solid-predominant tumor, 5-year recurrence-free survival after sublobar resection according to margin width ≤5 and >5 mm was 24.2 and 79.6 %, respectively (p < 0.001). Therefore, narrow margin width (resection margin ≤5 mm) was a significant risk factor for recurrence of solid-predominant tumors (hazard ratio 3.868, 95 % confidence interval 1.177-12.714, p = 0.026). CONCLUSIONS: The width between the tumor and resection margin does not affect the recurrence after R0 sublobar resection in patients with clinical N0 GGO-predominant lung cancer ≤3 cm. By contrast, margin width is a significant risk factor for recurrence after sublobar resection in patients with clinical N0 solid-predominant lung cancer.
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Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Margens de Excisão , Recidiva Local de Neoplasia/patologia , Idoso , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Feminino , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Estudos Retrospectivos , Fatores de RiscoRESUMO
Intractable or persistent hiccups require intensive or invasive treatments. The use of a phrenic nerve block or destructive treatment for intractable hiccups has been reported to be a useful and discrete method that might be valuable to patients with this distressing problem and for whom diverse management efforts have failed. We herein report a successful treatment using a removable and adjustable ligature for the phrenic nerve in a patient with recurrent and intractable hiccups, which was employed under the guidance of electromyography.
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Eletromiografia , Soluço/cirurgia , Bloqueio Nervoso/métodos , Procedimentos Neurocirúrgicos/métodos , Nervo Frênico/cirurgia , Cirurgia Assistida por Computador/métodos , Humanos , Ligadura/métodos , Masculino , Pessoa de Meia-Idade , Recidiva , Resultado do TratamentoRESUMO
Adenoid cystic carcinoma (ACC) is a relatively rare epithelial tumor of the salivary glands that accounts for approximately 5 to 10% of all salivary gland neoplasms. The typical clinical and pathological findings of this tumor include slow indolent growth, common local recurrence, and late distant metastasis to lung, brain, bone, liver, thyroid, and spleen. We report a 52-year-old female patient who presented a tongue ACC, 27 months after successful pulmonary ACC resection.
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Carcinoma Adenoide Cístico/patologia , Neoplasias Pulmonares/patologia , Metastasectomia/efeitos adversos , Neoplasias da Língua/secundário , Carcinoma Adenoide Cístico/cirurgia , Feminino , Humanos , Neoplasias Pulmonares/cirurgia , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Neoplasias da Língua/cirurgiaRESUMO
Background/Objectives: Pulmonary metastasis is the most prevalent type of extrahepatic hepatocellular carcinoma (HCC) metastasis. International guidelines recommend systemic treatment for patients with HCC having pulmonary metastases. However, the role of pulmonary metastasectomy (PM) remains relatively unexplored. Therefore, we assessed the survival outcomes and the factors influencing them in patients who underwent PM for metastatic HCC. Methods: Clinical data were collected from patients with HCC who underwent PM for metastasis at a single tertiary center between January 2004 and December 2022. Recurrence-free survival and overall survival were assessed using Kaplan-Meier curves. The Cox proportional hazards model was used to identify factors associated with survival outcomes. Results: Overall, 63 patients underwent PM with a median follow-up time of 84.0 months. The cumulative survival rates after the initial PM at 1, 2, and 5 years were 79.1%, 63.9%, and 35.6%, respectively. In multivariate analysis, early intrathoracic recurrence <6 months, number and size of metastases, resection margin status, and PM bilaterality were significantly associated with overall survival. A larger size of the primary HCC, increased number of repeated PM, and frequent lobectomy were more common in patients with early (<6 months) recurrence after PM than in those without early recurrence. Conclusions: PM in patients with metastatic HCC may provide acceptable survival outcomes for those with smaller, unilateral lung metastases that can be resected with generous surgical margins. However, early recurrence with reduced overall survival is likely in patients with a larger-size initial HCC after prior PM and lobectomy.
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Background: Early non-small cell lung cancer (NSCLC) that abuts adjacent structures requires careful evaluation due to its potential impact on postoperative outcomes and prognosis. We examined stage I NSCLC with invasion into adjacent structures, focusing on the prognostic implications after curative surgical resection. Methods: We retrospectively analyzed the records of 796 patients who underwent curative surgical resection for pathologic stage IA/IB NSCLC (i.e., visceral pleural invasion only) at a single center from 2008 to 2017. Patients were classified based on tumor abutment and then reclassified by the presence of visceral pleural invasion. Clinical characteristics, pathological features, and survival rates were compared. Results: The study included 181 patients with abutting NSCLC (22.7% of all participants) and 615 with non-abutting tumors (77.3%). Those with tumor abutment exhibited higher rates of non-adenocarcinoma (26.5% vs. 9.9%, p<0.01) and visceral/lymphatic/vascular invasion (30.4%/33.1%/12.7% vs. 8.5%/22.4%/5.7%, respectively; p<0.01) compared to those without abutment. Multivariable analysis identified lymphatic invasion and male sex as risk factors for overall survival (OS) and disease-free survival (DFS) in stage I NSCLC measuring 3 cm or smaller. Age, smoking history, vascular invasion, and recurrence emerged as risk factors for OS, whereas the presence of non-pure ground-glass opacity was a risk factor for DFS. Conclusion: NSCLC lesions 3 cm or smaller that abut adjacent structures present higher rates of various risk factors than non-abutting lesions, necessitating evaluation of tumor invasion into adjacent structures and lymph node metastasis. In isolation, however, the presence of tumor abutment without visceral pleural invasion does not constitute a risk factor.
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Background: Computed tomography (CT)-guided transthoracic needle biopsy (TNB) could damage lung structures and may disseminate tumor cells into the airway, blood vessels, and pleural cavity, affecting post-operative outcomes. Several studies have investigated the effects of TNB on the prognosis of patients, but the effects remain unclear. This study aimed to investigate whether TNB increases the risk of recurrence of resected stage IA non-small cell lung cancer (NSCLC). Methods: In this retrospective study, we enrolled 1,077 patients with stage IA NSCLC who underwent curative resection from 2010 to 2020. Recurrence risk factors were evaluated using Cox regression analyses. A multiple logistic regression model, including age, sex, smoking history, total tumor size, invasive tumor size, histology, histologic differentiation, lymphatic invasion, vascular invasion, perineural invasion, and the number of harvested lymph nodes (LNs), was used to calculate the propensity score. Results: According to the pre-operative TNB, patients were classified into the no-TNB (n=823) and TNB (n=190) groups. After propensity score matching analysis, 380 patients were included in the no-TNB group (1:2 matching). Multivariable Cox analysis revealed that pre-operative TNB was a negative prognostic factor in patients with surgically resected stage IA NSCLC [hazard ratio (HR), 3.15; 95% confidence interval (CI): 1.49-6.67; P=0.003]. The 5-year locoregional and overall recurrence-free survival (RFS) rates were significantly lower in the TNB group than in the no-TNB group (88.3% vs. 96.8%, P=0.001; and 84.2% vs. 93.7%, P=0.02, respectively). Conclusions: For patients with stage IA NSCLC, pre-operative TNB was a negative prognostic factor for recurrence. Surgical diagnosis and treatment without pre-operative tissue diagnosis may be considered first in patients with clinically early lung cancer.
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Background: Unexpected conversion to thoracotomy during planned video-assisted thoracoscopic surgery (VATS) can lead to poor outcomes and comparatively high morbidity. This study was conducted to assess preoperative risk factors associated with unexpected thoracotomy conversion and to develop a risk scoring model for preoperative use, aimed at identifying patients with an elevated risk of conversion. Methods: A retrospective analysis was conducted of 1,506 patients who underwent surgical resection for non-small cell lung cancer. To evaluate the risk factors, univariate analysis and logistic regression were performed. A risk scoring model was established to predict unexpected thoracotomy conversion during VATS of the lung, based on preoperative factors. To validate the model, an additional cohort of 878 patients was analyzed. Results: Among the potentially significant clinical variables, male sex, previous ipsilateral lung surgery, preoperative detection of calcified lymph nodes, and clinical T stage were identified as independent risk factors for unplanned conversion to thoracotomy. A 6-point risk scoring model was developed to predict conversion based on the assessed risk, with patients categorized into 4 groups. The results indicated an area under the receiver operating characteristic curve of 0.747, with a sensitivity of 80.5%, specificity of 56.4%, positive predictive value of 1.8%, and negative predictive value of 91.0%. When applied to the validation cohort, the model exhibited good predictive accuracy. Conclusion: We successfully developed and validated a risk scoring model for preoperative use that can predict the likelihood of unplanned conversion to thoracotomy during VATS of the lung.
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Background: Visceral pleural invasion (VPI) is a poor prognostic factor that contributes to the upstaging of early lung cancers. However, the preoperative assessment of VPI presents challenges. This study was conducted to examine intraoperative pleural carcinoembryonic antigen (pCEA) level and maximum standardized uptake value (SUVmax) as predictive markers of VPI in patients with clinical T1N0M0 lung adenocarcinoma. Methods: A retrospective review was conducted of the medical records of 613 patients who underwent intraoperative pCEA sampling and lung resection for non-small cell lung cancer. Of these, 390 individuals with clinical stage I adenocarcinoma and tumors ≤30 mm were included. Based on computed tomography findings, these patients were divided into pleural contact (n=186) and non-pleural contact (n=204) groups. A receiver operating characteristic (ROC) curve was constructed to analyze the association between pCEA and SUVmax in relation to VPI. Additionally, logistic regression analysis was performed to evaluate risk factors for VPI in each group. Results: ROC curve analysis revealed that pCEA level greater than 2.565 ng/mL (area under the curve [AUC]=0.751) and SUVmax above 4.25 (AUC=0.801) were highly predictive of VPI in patients exhibiting pleural contact. Based on multivariable analysis, pCEA (odds ratio [OR], 3.00; 95% confidence interval [CI], 1.14-7.87; p=0.026) and SUVmax (OR, 5.25; 95% CI, 1.90-14.50; p=0.001) were significant risk factors for VPI in the pleural contact group. Conclusion: In patients with clinical stage I lung adenocarcinoma exhibiting pleural contact, pCEA and SUVmax are potential predictive indicators of VPI. These markers may be helpful in planning for lung cancer surgery.
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This study proposed an optimized histogel construction method for histological analysis by applying lung cancer patient-derived organoids (PDOs) to the developed histo-pillar strip. Previously, there is the cultured PDOs damage problem during the histogel construction due to forced detachment of the Matrigel spots from the 96-well plate bottom. To address this issue, we cultured PDO on the proposed Histo-pillar strips and then immersed them in 4% paraformaldehyde fixation solution to self-isolate PDO without damage. The 4µl patient-derived cell (PDC)/Matrigel mixtures were dispensed on the surface of a U-shaped histo-pillar strip, and the PDCs were aggregated by gravity and cultured into PDOs. Cultured PDOs were self-detached by simply immersing them in a paraformaldehyde fixing solution without physical processing, showing about two times higher cell recovery rate than conventional method. In addition, we proposed a method for embedding PDOs under conditions where the histogel temperature was maintained such that the histogel did not harden, thereby improving the problem of damaging the histogel block in the conventional sandwich histogel construction method. We performed histological and genotyping analyses using tumor tissues and PDOs from two patients with lung adenocarcinoma. Therefore, the PDO culture and improved histogel block construction method using the histo-pillar strip proposed in this study can be employed as useful tools for the histological analysis of a limited number of PDCs.
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Neoplasias Pulmonares , Organoides , Humanos , Organoides/metabolismo , Organoides/efeitos dos fármacos , Organoides/patologia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/metabolismo , Biomarcadores Tumorais/metabolismo , Laminina/química , Géis/química , Colágeno/química , Colágeno/metabolismo , Combinação de Medicamentos , Proteoglicanas/químicaRESUMO
Patient-derived organoids (PDOs) are valuable in predicting response to cancer therapy. PDOs are ideal models for precision oncologists. However, their practical application in guiding timely clinical decisions remains challenging. This study focused on patients with advanced EGFR-mutated non-small cell lung cancer and employed a cancer organoid-based diagnosis reactivity prediction (CODRP)-based precision oncology platform to assess the efficacy of EGFR inhibitor treatments. CODRP was employed to evaluate EGFR-tyrosine kinase inhibitors (TKI) drug sensitivity. The results were compared to those obtained using area under the curve index. This study validated this index by testing lung cancer-derived organoids in 14 patients with lung cancer. The CODRP index-based drug sensitivity test reliably classified patient responses to EGFR-TKI treatment within a clinically suitable 10-day timeline, which aligned with clinical drug treatment responses. This approach is promising for predicting and analyzing the efficacy of anticancer, ultimately contributing to the development of a precision medicine platform.
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We report a new surgical technique for spontaneous esophagopleural fistula after pneumonectomy. A 67-year-old man underwent right pneumonectomy for tuberculosis-destroyed lung 30 years previously and a right Eloesser window for empyema without any evidence of fistula 4 years previously. He presented to our hospital for food material spillage out of the Eloesser window when he was eating. The esophagopleural fistula was observed from the upper thoracic esophagus to the right postpneumonectomy dead space. He underwent left cervical esophagogastrostomy via a presternal subcutaneous route, using thoracic esophageal mucosal stripping. He was discharged without complications on postoperative day 12.
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Fístula Esofágica/cirurgia , Esofagostomia , Fístula/cirurgia , Gastrostomia , Doenças Pleurais/cirurgia , Pneumonectomia/efeitos adversos , Tuberculose Pulmonar/cirurgia , Idoso , Fístula Esofágica/diagnóstico , Fístula Esofágica/etiologia , Fístula/diagnóstico , Fístula/etiologia , Humanos , Masculino , Mucosa/cirurgia , Doenças Pleurais/diagnóstico , Doenças Pleurais/etiologia , Reoperação , Resultado do TratamentoRESUMO
An 8-year-old male presented with a cystic lung lesion in the left lower lobe, which was initially detected during surgery for a spontaneous rupture of the sigmoid colon at the age of 6 years. Tissue fragility and a tendency to bleed easily were noted during the surgery, which strongly suggested vascular Ehlers-Danlos syndrome. Although there was no abnormality in the hemostasis screening test, or any suspicious hereditary problem in his pedigree, genetic gene testing for vascular Ehlers-Danlos syndrome was recommended, and showed a de novo mutation in the COL3A1 gene. This report presents the case of patient with occlusive vascular Ehlers-Danlos syndrome accompanying a congenital cystic adenomatoid malformation of lung, in addition to a duplicated infrarenal vena cava.
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Malformação Adenomatoide Cística Congênita do Pulmão/diagnóstico , Malformação Adenomatoide Cística Congênita do Pulmão/cirurgia , Síndrome de Ehlers-Danlos/diagnóstico , Síndrome de Ehlers-Danlos/cirurgia , Criança , Colágeno Tipo III/genética , Malformação Adenomatoide Cística Congênita do Pulmão/complicações , Malformação Adenomatoide Cística Congênita do Pulmão/patologia , Síndrome de Ehlers-Danlos/complicações , Síndrome de Ehlers-Danlos/genética , Humanos , Achados Incidentais , Rim/irrigação sanguínea , Masculino , Mutação , Ruptura Espontânea , Doenças do Colo Sigmoide/etiologia , Doenças do Colo Sigmoide/cirurgia , Tomografia Computadorizada por Raios X , Veia Cava Inferior/anormalidadesRESUMO
Background: Given the heterogeneity of underlying lung disease and the higher morbidity and mortality associated with surgery for secondary pneumothorax (SP), treatment standardization and evidence-based early surgical management are challenging pursuits. Our aim was to document the clinical course of SP after initial surgical intervention and analyse related recurrence risk. Methods: We conducted a retrospective review of 160 patients, each with SP, using clinical records housed in an institutional database. Clinical, imaging, and operative data were retrieved, and Cox proportional hazards (PH) analysis was undertaken to identify risk factors for recurrence. Results: During a mean follow-up of 58.7 months, the overall recurrence rate in this cohort was 18.75% (ipsilateral, 14; contralateral, 16). A total of 24 patients had ≥3 ipsilateral episodes <6 months prior to surgery, marked by initial index episodes. In multivariate Cox PH analysis, the strongest risk factor for recurrence was underlying lung pathology other than chronic obstructive pulmonary disease [COPD: hazard ratio (HR) =5.3; P<0.001]. Conclusions: In this setting, underlying lung disease of a non-COPD nature is a proven risk factor for postsurgical recurrence. There is also a tendency in some patients for multiple episodes of pneumothorax within short periods of time, especially in the absence of COPD. Underlying disease processes may thus merit consideration in treatment planning.
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The metabolic profile of cancerous cells is shifted to meet the cellular demand required for proliferation and growth. Here we show the features of cancer metabolic profiles using peripheral blood of healthy control subjects (n = 78) and lung adenocarcinoma (LUAD) patients (n = 64). Among 121 detected metabolites, diagnosis of LUAD is based on arginine, lysophosphatidylcholine-acyl (Lyso.PC.a) C16:0, and PC-diacyl (PC.aa) C38:3. Network analysis revealed that network heterogeneity, diameter, and shortest path were decreased in LUAD. On the contrary, these parameters were increased in advanced-stage compared to early-stage LUAD. Clustering coefficient, network density, and average degree were increased in LUAD compared to the healthy control, whereas these topologic parameters were decreased in advanced-stage compared to early-stage LUAD. Public LUAD data verified that the genes encoding enzymes for arginine (NOS, ARG, AZIN) and for Lyso.PC and PC (CHK, PCYT, LPCAT) were related with overall survival. Further studies are required to verify these results with larger samples and other histologic types of lung cancer.
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Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Humanos , Prognóstico , Perfilação da Expressão Gênica , Biomarcadores Tumorais/genética , Adenocarcinoma de Pulmão/genética , Neoplasias Pulmonares/genéticaRESUMO
BACKGROUND: Recently, cancer organoid-based drug sensitivity tests have been studied to predict patient responses to anticancer drugs. The area under curve (AUC) or IC50 value of the dose-response curve (DRC) is used to differentiate between sensitive and resistant patient's groups. This study proposes a multi-parameter analysis method (cancer organoid-based diagnosis reactivity prediction, CODRP) that considers the cancer stage and cancer cell growth rate, which represent the severity of cancer patients, in the sensitivity test. METHODS: On the CODRP platform, patient-derived organoids (PDOs) that recapitulate patients with lung cancer were implemented by applying a mechanical dissociation method capable of high yields and proliferation rates. A disposable nozzle-type cell spotter with efficient high-throughput screening (HTS) has also been developed to dispense a very small number of cells due to limited patient cells. A drug sensitivity test was performed using PDO from the patient tissue and the primary cancer characteristics of PDOs were confirmed by pathological comparision with tissue slides. RESULTS: The conventional index of drug sensitivity is the AUC of the DRC. In this study, the CODRP index for drug sensitivity test was proposed through multi-parameter analyses considering cancer cell proliferation rate, the cancer diagnosis stage, and AUC values. We tested PDOs from eight patients with lung cancer to verify the CODRP index. According to the anaplastic lymphoma kinase (ALK) rearrangement status, the conventional AUC index for the three ALK-targeted drugs (crizotinib, alectinib, and brigatinib) did not classify into sensitive and resistant groups. The proposed CODRP index-based drug sensitivity test classified ALK-targeted drug responses according to ALK rearrangement status and was verified to be consistent with the clinical drug treatment response. CONCLUSIONS: Therefore, the PDO-based HTS and CODRP index drug sensitivity tests described in this paper may be useful for predicting and analyzing promising anticancer drug efficacy for patients with lung cancer and can be applied to a precision medicine platform.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Crizotinibe/uso terapêutico , OrganoidesRESUMO
BACKGROUND: Preoperative localization is frequently necessary to perform thoracoscopic resection of a small and/or deeply located intrapulmonary lesion. We developed a new method that uses a fragmented platinum microcoil, and retrospectively evaluated the efficacy of our technique. METHODS: Between January 2006 and May 2010, self-made microcoils (Easimarker) were used to localize total 32 lesions (21 solid nodules, and 11 ground glass opacities) in 30 patients. Computed tomography-guided localization was performed into, or just around the lesions. Localized lesions were resected using fluoroscopy-assisted thoracoscopic surgery (FATS), and the histopathologic diagnosis was confirmed. The accuracy and complications of the localization procedure, and operative results of FATS were observed. RESULTS: Mean size and depth of all lesions were 11.8 ± 5.1 mm (range: 3 to 22) and 12.2 ± 7.1 mm (range: 2 to 30). CT-guided localizations were successfully performed in all lesions. Four minimal pneumothorax and one parenchymal hematoma related with localization procedure occurred. There were three repeated procedures, which resulted from pleural rebounding of the microcoils. There were two microcoil detecting failures due to intrathoracic displacement during FATS. All 32 resected lesions were histopathologically diagnosed. CONCLUSION: CT-guided localization using the fragmented microcoil combined with FATS of small intrapulmonary lesions is a safe, effective, and a diagnostically accurate procedure.