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1.
Respirology ; 28(7): 669-676, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37106570

RESUMO

BACKGROUND AND OBJECTIVE: Although stage I non-small cell lung carcinoma (NSCLC) typically carries a good prognosis following complete resection, early disease recurrence can occur. An accurate survival prediction model would help refine a follow-up strategy and personalize future adjuvant therapy. We developed a post-operative prediction model based on readily available clinical information for patients with stage I adenocarcinoma. METHODS: We retrospectively studied the disease-free survival (DFS) of 408 patients with pathologically confirmed low-risk stage I adenocarcinoma of lung who underwent curative resection from 2013 to 2017. A tree-based method was employed to partition the cohort into subgroups with distinct DFS outcome and stepwise risk ratio. These covariates were included in multivariate analysis to build a scoring system to predict disease recurrence. The model was subsequently validated using a 2011-2012 cohort. RESULTS: Non-smoker status, stage IA disease, epidermal-growth factor receptor mutants and female gender were associated with better DFS. Multivariate analysis identified smoking status, disease stage and gender as factors necessary for the scoring system and yielded 3 distinct risk groups for DFS [99.4 (95% CI 78.3-125.3), 62.9 (95% CI 48.2-82.0), 33.7 (95% CI 24.6-46.1) months, p < 0.005]. External validation yielded an area under the curve by receiver operating characteristic analysis of 0.863 (95% CI 0.755-0.972). CONCLUSION: The model could categorize post-operative patients using readily available clinical information, and may help personalize a follow-up strategy and future adjuvant therapy.


Assuntos
Adenocarcinoma de Pulmão , Adenocarcinoma , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Estudos Retrospectivos , Estadiamento de Neoplasias , Recidiva Local de Neoplasia/epidemiologia , Adenocarcinoma de Pulmão/cirurgia , Adenocarcinoma de Pulmão/patologia , Adenocarcinoma/cirurgia , Adenocarcinoma/patologia , Prognóstico
2.
Respirology ; 25 Suppl 2: 61-71, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32516852

RESUMO

Radiotherapy is an important modality used for the treatment of lung cancer. Seventy-seven percent of all patients with lung cancer have an evidence-based indication for radiotherapy, although it is often underutilized. Radiotherapy can be used as curative or palliative treatment across all stages of disease. Technological advances have allowed better radiotherapy targeting of tumours and reduced incidental irradiation of surrounding normal tissues. This has expanded the indications for radiotherapy in lung cancer and improved outcomes both in terms of increasing survival and reducing toxicity. This review examines the current role of radiotherapy in lung cancer, discusses the evidence behind this and identifies future directions in the radiotherapy treatment of lung cancer.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/radioterapia , Neoplasias Pulmonares/radioterapia , Carcinoma Pulmonar de Células não Pequenas/patologia , Terapia Combinada , Humanos , Neoplasias Pulmonares/patologia , Estadiamento de Neoplasias , Cuidados Paliativos , Radioterapia/efeitos adversos , Radioterapia/métodos
3.
Arkh Patol ; 82(6): 24-28, 2020.
Artigo em Russo | MEDLINE | ID: mdl-33274622

RESUMO

Neural network analysis of digital copies of histological micropreparations is one of the methods used to standardize quantitative continuous data. PD-L1 (22C3) biomarker expression in metastatic non-small cell lung carcinomas without mutations in the EGFR, ALK, and ROS1 genes serves as an indication for the use of pembrolizumab for the first-line therapy. OBJECTIVE: To quantify PD-L1 biomarker expression in non-small cell lung carcinomas using the neural network analysis of digital copies of histological micropreparations. MATERIAL AND METHODS: Immunohistochemical study of PD-L1 (22C3) expression was performed on 96 non-small cell lung carcinoma biopsy specimens. The digital copies of histological micropreparations were processed by the QuPath software neural network analysis module. RESULTS: The neural network analysis module segmented tumor, stroma, and artifacts in the micropreparations, showing a sufficient level of agreement with a visual assessment. Digital image analysis quantified stained tumor cells in the high PD-L1 expression group and showed 96% agreement rate versus visual assessment. However, the group of tumors without PD-L1 expression versus visual assessment showed a low (58%) agreement rate. CONCLUSION: The neural network analysis algorithm is applicable to the study of digital copies of histological micropreparations containing tumor, stroma, and artifacts. The algorithm allows for quantitative immunohistochemical assessment of PD-L1 expression in tumor cells. The algorithm can quantify the immunohistochemically detected expression of PD-L1 in tumor cells.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Antígeno B7-H1 , Biomarcadores Tumorais , Biópsia , Humanos , Redes Neurais de Computação , Proteínas Tirosina Quinases , Proteínas Proto-Oncogênicas
4.
Mol Carcinog ; 58(7): 1168-1180, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30834575

RESUMO

Ras-association domain family (RASSF) proteins exert distinct cellular functions. The expression of RASSF10 in non-small cell lung cancer and its underlying mechanism have not been reported. Herein, we explored the roles of RASSF10 in lung cancer cells and potential molecular mechanisms. We found low RASSF10 expression in lung cancer specimens, which was associated with low differentiation, advanced pTNM stage, positive lymph node metastasis, and poor prognosis in patients. Furthermore, RASSF10 overexpression inhibited the proliferation and invasion of lung cancer cells, which was the result of Wnt signaling suppression. However, we found that RASSF10 had no influence on Hippo signaling, while RASSF10 bound to LRP6 via the coiled-coil domains and reduced p-LRP6 level, eventually prohibiting ß-catenin nuclear translocation. However, deleting the coiled-coil domains ablated this function. These findings expound the interaction between RASSF10 and LRP6 and uncover a potential link between N-terminal RASSFs and the Wnt pathway.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/patologia , Proteína-6 Relacionada a Receptor de Lipoproteína de Baixa Densidade/metabolismo , Neoplasias Pulmonares/patologia , Proteínas Supressoras de Tumor/genética , Via de Sinalização Wnt/genética , Células A549 , Transporte Ativo do Núcleo Celular/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Linhagem Celular Tumoral , Proliferação de Células/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Células HEK293 , Via de Sinalização Hippo , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidade , Metástase Linfática/patologia , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/genética , Fosforilação/genética , Prognóstico , Ligação Proteica/genética , Proteínas Serina-Treonina Quinases/metabolismo , beta Catenina/metabolismo
5.
Cytopathology ; 30(6): 601-606, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31273868

RESUMO

BACKGROUND: Current therapy requires separation of non-small cell carcinomas into adenocarcinomas (AC) and squamous cell carcinomas (SCC). A meta-analysis has shown a pooled diagnostic sensitivity of 63% and specificity of 95% for the diagnosis of AC. While a number of cytomorphological features have been proposed for separation of AC from SCC, we are unaware of a statistically based analysis of cytomorphological features useful for separation of these two carcinomas. We performed logistic regression analysis of cytological features useful in classifying SCC and AC. DESIGN: Sixty-one Papanicolaou-stained fine needle aspiration specimens (29 AC/32 SCC) were reviewed by two board-certified cytopathologists for nine features (eccentric nucleoli, vesicular chromatin, prominent nucleoli, vacuolated cytoplasm, 3-dimensional cell balls, dark non-transparent chromatin, central nucleoli, single malignant cells and spindle-shaped cells). All cytological specimens had surgical biopsy results. Inter-rater agreement was assessed by Cohen's κ. Association between features and AC was determined using hierarchical logistic regression model where feature scores were nested within reviewers. A model to classify cases as SCC or AC was developed and verified by k-fold verification (k = 5). Classification performance was assessed using the area under the receiver operating characteristic curve. RESULTS: Observed rater agreement for scored features ranged from 49% to 82%. Kappa scores were clustered in three groups. Raters demonstrated good agreement for prominent nucleoli, vesicular chromatin and eccentric nuclei. Fair agreement was seen for 3-dimensional cell balls, dark non-transparent chromatin, and presence of spindle-shaped cells. Association of features with adenocarcinoma showed four statistically significant associations (P < 0.001) with adenocarcinoma. These features were prominent nucleoli, vesicular chromatin, eccentric nuclei and three-dimensional cell balls. Spindle-shaped cells and dark non-transparent chromatin were negatively associated with adenocarcinoma. CONCLUSIONS: Logistic regression analysis demonstrated six features helpful in separation of AC from SCC. Prominent nucleoli, vesicular chromatin, cell balls and eccentric nucleoli were positively associated with AC and demonstrated a P value of 0.001 or less. The presence of dark, non-transparent chromatin and spindle-shaped cells favoured the diagnosis of SCC.


Assuntos
Adenocarcinoma de Pulmão/patologia , Carcinoma de Células Escamosas/patologia , Citodiagnóstico , Diagnóstico Diferencial , Adenocarcinoma de Pulmão/classificação , Adenocarcinoma de Pulmão/diagnóstico , Biópsia por Agulha Fina , Carcinoma de Células Escamosas/classificação , Carcinoma de Células Escamosas/diagnóstico , Nucléolo Celular , Núcleo Celular , Feminino , Humanos , Masculino , Medicina de Precisão
6.
Cancer Sci ; 109(8): 2532-2538, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29807396

RESUMO

Epidermal growth factor receptor (EGFR) activating mutations occur in approximately 50% of East Asian patients with non-small-cell lung cancer (NSCLC) and confer sensitivity to tyrosine kinase inhibitors (TKIs). ASP8273 is an irreversible EGFR-TKI, given orally, that inhibits EGFR activating mutations and has shown clinical activity in patients with EGFR mutation-positive NSCLC. Epidermal growth factor receptor-TKI-naïve Japanese adult patients (≥20 years) with NSCLC harboring EGFR mutations were enrolled in this open-label, single-arm, phase II study (ClinicalTrials.gov identifier NCT02500927). Patients received ASP8273 300 mg once daily until discontinuation criteria were met. The primary end-point was to determine the safety of ASP8273 300 mg; the secondary end-point was antitumor activity defined by RECIST version 1.1. Thirty-one patients (12 men and 19 women; median age, 64 years [range, 31-82 years]) with EGFR mutation-positive NSCLC were enrolled; as of 23 February 2016, 25 patients (81%) were still on study. Of the 31 patients, 27 (87%) had an exon 19 deletion (n = 13, 42%) or an L858R (n = 14, 45%) EGFR activating mutation, and two (7%) had an L861Q mutation. Five patients (16%) had other EGFR activating mutations, two had an activating mutation and the T790M resistance mutation. The most commonly reported treatment-emergent adverse event was diarrhea (n = 24, 77%). All patients had at least one post-baseline scan; one patient (3%) achieved a confirmed complete response, 13 (42%) had a confirmed partial response, and 15 (48%) had confirmed stable disease (disease control rate, 94% [n = 29/31]) per investigator assessment. Once-daily ASP8273 at 300 mg was generally well tolerated and showed antitumor activity in TKI-naïve Japanese patients with EGFR mutation-positive NSCLC.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Receptores ErbB/genética , Neoplasias Pulmonares/tratamento farmacológico , Mutação/genética , Piperazinas/uso terapêutico , Piperidinas/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Pirazinas/uso terapêutico , Pirrolidinas/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Povo Asiático , Carcinoma Pulmonar de Células não Pequenas/genética , Intervalo Livre de Doença , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Humanos , Neoplasias Pulmonares/genética , Masculino , Pessoa de Meia-Idade
7.
Cancer Sci ; 109(9): 2852-2862, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29972716

RESUMO

Epidermal growth factor receptor (EGFR)-activating mutations confer sensitivity to tyrosine kinase inhibitor (TKI) treatment for non-small-cell lung cancer (NSCLC). ASP8273 is a highly specific, irreversible, once-daily, oral, EGFR TKI that inhibits both activating and resistance mutations. This ASP8273 dose-escalation/dose-expansion study (NCT02192697) was undertaken in two phases. In phase I, Japanese patients (aged ≥20 years) with NSCLC previously treated with ≥1 EGFR TKI received escalating ASP8273 doses (25-600 mg) to assess safety/tolerability and to determine the maximum tolerated dose (MTD) and/or the recommended phase II dose (RP2D) by the Bayesian Continual Reassessment Method. In phase II, adult patients with T790M-positive NSCLC in Japan, Korea, and Taiwan received ASP8273 at RP2D to further assess safety/tolerability and determine antitumor activity, which was evaluated according to Simon's two-stage design (threshold response = 30%, expected response = 50%, α = 0.05, ß = 0.1). Overall, 121 (n = 45 [33W/12M] phase I, n = 76 [48W/28M]) phase 2) patients received ≥1 dose of ASP8273. In phase I, RP2D and MTD were established as 300 and 400 mg, respectively. As 27 of the 63 patients treated with ASP8273 300 mg achieved a clinical response, ASP8273 was determined to have antitumor activity. The overall response rate at week 24 in all patients was 42% (n = 32/76; 95% confidence interval, 30.9-54.0). Median duration of progression-free survival was 8.1 months (95% confidence interval, 5.6, upper bound not reached). The most commonly reported treatment-related adverse event in phase II was diarrhea (57%, n = 43/76). ASP8273 300 mg was generally well tolerated and showed antitumor activity in Asian patients with both EGFR-activating and T790M mutations.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Receptores ErbB/antagonistas & inibidores , Neoplasias Pulmonares/tratamento farmacológico , Mutação , Piperazinas/uso terapêutico , Piperidinas/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Pirazinas/uso terapêutico , Pirrolidinas/uso terapêutico , Adulto , Idoso , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Receptores ErbB/genética , Feminino , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Piperazinas/efeitos adversos , Piperazinas/farmacocinética , Piperidinas/efeitos adversos , Piperidinas/farmacocinética , Pirazinas/efeitos adversos , Pirazinas/farmacocinética , Pirrolidinas/efeitos adversos , Pirrolidinas/farmacocinética
8.
Am J Respir Crit Care Med ; 193(3): 321-9, 2016 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-26436758

RESUMO

RATIONALE: The goal of shared decision making is to match patient preferences, including evaluation of potential future outcomes, with available management options. Yet, it is unknown how patients with smoking-related thoracic diseases or their surrogates display future-oriented thinking. OBJECTIVES: To document prevalent themes in patients' and potential surrogate decision makers' future-oriented thinking when facing preference-sensitive choices. METHODS: We conducted 44 scenario-based semistructured interviews among a diverse group of outpatients with smoking-associated thoracic diseases and potential surrogates for whom one of three preference-sensitive decisions would be medically relevant. Using content analysis, we documented prevalent themes to understand how these individuals display future-oriented thinking. MEASUREMENTS AND MAIN RESULTS: Patients and potential surrogates generally expressed expectations for future outcomes but also acknowledged their limitations in doing so. When thinking about potential outcomes, decision makers relied on past experiences, including those only loosely related; perceived familiarity with treatment options; and spirituality. The content of these expectations included effects on family, emotional predictions, and prognostication. For surrogates, a tension existed between hope-based and fact-based expectations. CONCLUSIONS: Patients and surrogates may struggle to generate expectations, and these future-oriented thoughts may be based on loosely related past experiences or unrealistic optimism. These tendencies may lead to errors, preventing selection of treatments that promote true preferences. Clinicians should explore how decision makers engage in future-oriented thinking and what their expectations are as a component of the shared decision-making process. Future research should evaluate whether targeted guidance in future-oriented thinking may improve outcomes important to patients.


Assuntos
Fumar/efeitos adversos , Fumar/psicologia , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/etiologia , Carcinoma Pulmonar de Células não Pequenas/psicologia , Cuidadores/psicologia , Tomada de Decisões , Feminino , Humanos , Entrevista Psicológica , Neoplasias Pulmonares/etiologia , Neoplasias Pulmonares/psicologia , Masculino , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/etiologia , Doença Pulmonar Obstrutiva Crônica/psicologia , Pensamento
9.
Ann Pathol ; 36(1): 44-54, 2016 Jan.
Artigo em Francês | MEDLINE | ID: mdl-26778815

RESUMO

Pulmonary sarcomatoid carcinomas are a rare group of tumors accounting for about one percent of non-small cell lung carcinoma (NSCLC). In 2015, the World Health Organization classification united under this name all the carcinomas with sarcomatous-like component with spindle cell or giant cell appearance, or associated with a sarcomatous component sometimes heterologous. There are five subtypes: pleomorphic carcinoma, spindle cell carcinoma, giant cell carcinoma, carcinosarcoma and pulmonary blastoma. Clinical characteristics are not specific from the other subtypes of NSCLC. Epithelial to mesenchymal transition pathway may play a key role. Patients, usually tobacco smokers, are frequently symptomatic. Tumors are voluminous more often peripherical than central, with strong fixation on FDG TEP CT. Distant metastases are frequent with atypical visceral locations. These tumors have poorer prognosis than the other NSCLC subtypes because of great aggressivity, and frequent chemoresistance. Here we present pathological description and a review of literature with molecular features in order to better describe these tumors and perhaps introduce new therapeutics.


Assuntos
Carcinoma/classificação , Neoplasias Pulmonares/classificação , Biomarcadores Tumorais , Carcinoma/química , Carcinoma/diagnóstico por imagem , Carcinoma/epidemiologia , Carcinoma/patologia , Diferenciação Celular , Diagnóstico Diferencial , Transição Epitelial-Mesenquimal , Humanos , Neoplasias Pulmonares/química , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/patologia , Prognóstico
10.
Semin Diagn Pathol ; 32(5): 325-33, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25753527

RESUMO

Most clinically actionable alterations in lung adenocarcinomas are detected using molecular or cytogenetic techniques. However, many such alterations have a protein-level correlate that can be interrogated using immunohistochemistry. This review will summarize the therapeutic relevance of predictive biomarkers in lung adenocarcinoma including the oncogenes EGFR, MET, ALK, RET, and ROS1 and tumor suppressors PTEN and LKB1 with an emphasis on established and emerging protein immunohistochemistry reagents and their promise in clinical practice.


Assuntos
Adenocarcinoma/genética , Biomarcadores Tumorais/genética , Imuno-Histoquímica , Neoplasias Pulmonares/genética , Proteínas de Neoplasias/genética , Adenocarcinoma/química , Adenocarcinoma/patologia , Adenocarcinoma de Pulmão , Predisposição Genética para Doença , Humanos , Neoplasias Pulmonares/química , Neoplasias Pulmonares/patologia , Técnicas de Diagnóstico Molecular , Fenótipo , Valor Preditivo dos Testes , Prognóstico
11.
J Immunoassay Immunochem ; 36(2): 111-8, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-24689794

RESUMO

Despite the new available histologic classification of lung cancers, it remains difficult to assess the real prognostic relevance of the different subtypes of lung adenocarcinomas. Facing the prognostic relevance of microvessel density (MVD) and the expression of metalloproteases and thyroid tyrosine factor 1 (TTF1) in different cancers, we tried to compare these parameters in the different subtypes of lung adenocarcinomas. We conducted a retrospective study of 46 adenocarcinomas surgically resected. An immunohistochemical study using the cluster of differentiation 34 (CD34), TTF1, metalloproteases 2 (MMP2), and metalloproteases 9 (MMP9) antibodies was performed on all samples while MVD was evaluated using CD34 antibody. The analyzed cases included 19 acinar, 7 papillary, 1 lepidic, and 19 solid predominant American Thoracic Classification of lung adenocarcinomas (ASK). The higher MVD levels were observed in papillary and acinar subtypes types and a statically significant difference in the MVD was observed in the different subtypes (p< 0,001). This study didn't show significant statistical results concerning MMP and TTF1 expression but it revealed a tendency to an equal expression of these antibodies in the different subtypes. The difference in the MVD between the different subtypes of adenocarcinoma puts emphasis on their prognostic relevance.


Assuntos
Adenocarcinoma , Neoplasias Pulmonares , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Microvasos/patologia , Proteínas Nucleares/metabolismo , Fatores de Transcrição/metabolismo , Adenocarcinoma/classificação , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Adenocarcinoma de Pulmão , Adulto , Idoso , Antígenos CD34/metabolismo , Feminino , Humanos , Neoplasias Pulmonares/classificação , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Fator Nuclear 1 de Tireoide , Tunísia
12.
Histopathology ; 65(6): 868-78, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25130792

RESUMO

AIMS: Need for accurate histologic subtyping of non-small cell lung carcinomas (NSCLCs) is growing. IHC patterns may be ambiguous in some cases, rendering it difficult to determine subtypes. METHODS AND RESULTS: Tissue microarrays composed of 184 resected NSCLCs were stained for TTF-1, Napsin A, CK7, p40, p63, CK5/6, and mucicarmine. TTF-1 and Napsin A were chosen as the most accurate adenocarcinoma (ADC) marker (ACM), and p40 as squamous cell carcinoma (SCC) marker (SCM). We then prospectively performed IHC using these markers (TTF-1, Napsin A, and p40) in a cohort of small NSCLC biopsies (n = 186) with ambiguous morphology. Of these biopsies, 82.8% (154/186) were classifiable into either ADC or SCC by applying '3-marker IHC panel'. Additional CK7, p63, and CK5/6 were applied in 30 biopsies with equivocal IHC patterns, including 18 ACM-/SCM- (double-negative) and 12 ACM+/SCM+ (double-positive) cases. Decision tree and support vector machine models revealed that TTF-1 was a critical single marker for ADC in double-positive cases (91.7% accuracy), whereas p63 and/or CK5/6 helped to subtype double-negative cases (72.2% accuracy). CONCLUSIONS: We propose a novel comprehensive algorithm for subtyping NSCLCs using a 3-marker IHC panel and additional p63 and CK5/6 that would be useful for subtyping small NSCLC biopsies.


Assuntos
Algoritmos , Biomarcadores Tumorais/análise , Carcinoma Pulmonar de Células não Pequenas/classificação , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/classificação , Neoplasias Pulmonares/patologia , Biópsia , Árvores de Decisões , Humanos , Imuno-Histoquímica , Sensibilidade e Especificidade , Máquina de Vetores de Suporte , Análise Serial de Tecidos
13.
Cureus ; 16(2): e54677, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38523986

RESUMO

Electrical alternans on electrocardiograph (ECG) is an uncommon but nearly pathognomonic sign of cardiac tamponade. Here, we present a male quadragenarian who came to the emergency department complaining of low back and right upper abdominal pain. Work-up revealed a large pericardial effusion associated with electrical alternans on ECG and clinical findings of cardiac tamponade. Pericardiocentesis drained approximately 1 liter of hemorrhagic fluid with resolution of cardiac tamponade and normalization of the ECG. Further evaluation with right hilar lymph node biopsy confirmed a diagnosis of poorly differentiated non-small cell adenocarcinoma of the lung.

14.
Heliyon ; 10(5): e27147, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38495135

RESUMO

Background: Forkhead box M1 (FOXM1) functions as a transcription factor and is consistently overexpressed in various cancers, including non-small-cell lung-, breast-, cervical-, and colorectal cancer. Its overexpression is associated with poor prognosis in patients with non-small-cell lung cancer, although the detailed mechanisms by which FOXM1 promotes the development of non-small-cell lung cancer remain unclear. Objective: The mechanism of FOXM1 in migration, invasion, apoptosis, and viability of lung cancer cells was investigated. Methods: Transwell assay, scratch test, and flow cytometry were employed to study the effects of FOXM1 on migration, invasion, and apoptosis in A549 cells. A quantitative polymerase chain reaction was used to determine the impact of FOXM1 on miR-509-5p expression in A549 cells. Dual-luciferase reporter gene assay and chromatin immunoprecipitation were adopted to investigate the molecular mechanisms of FOXM1 on miR-509-5p expression. Results: FDI-6 (a FOXM1 inhibitor) reduced the protein abundance of FOXM1, thereby increasing the expression of miR-509-5p in A549 cells. Moreover, FDI-6 treatment significantly reduced migration, invasion, and viability of A549 cells while promoting cell apoptosis. Furthermore, miR-509-5p inhibitor obviously alleviated the biological effects of FDI-6 on A549 cells, suggesting that FOXM1 primarily exerted its cancer promoting effect by regulating miR-509-5p. Mechanistically, FOXM1 directly bound to the miR-509-5p promoter to inhibit miR-509-5p expression. Conclusion: FOXM1 directly binds to the promoter region of miR-509-5p to form a negative feedback loop, thereby inhibiting miR-509-5p expression and promoting the development of non-small-cell lung cancer. This study is expected to complement research on the pathogenesis of non-small-cell lung cancer and promote the development of novel therapeutic targets for this disease.

15.
J Am Soc Cytopathol ; 13(5): 340-345, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38797657

RESUMO

INTRODUCTION: There is an increasing demand to optimize the workflow and maximize tissue available for next-generation sequencing (NGS) for non-small cell carcinoma. We looked at transbronchial needle endobronchial ultrasound-guided bronchoscopy with transbronchial needle aspiration samples and evaluated the performance of supernatant (SN) fluid processed from a dedicated aspirate collected for NGS testing. MATERIALS AND METHODS: Nineteen samples were collected and processed using a new workflow. Five aspirates were collected in formalin. One additional dedicated pass was collected fresh and centrifuged. The resulting cell pellet was added to formalin for cell block (CB) processing. DNA and RNA were extracted from concentrated SN for targeted testing using the Oncomine Precision Assay (Thermo Scientific, Waltham, MA). NGS results from the corresponding CB samples were used as "controls" for comparison. RESULTS: Thirty-one mutations were detected in SN (Table 1). The most frequently mutated genes were TP53 (35%), EGFR (23%), KRAS (13%), CTNNB1 (6%), and ERBB2 (6%). There was 100% concordance between the mutations detected in SN and corresponding CBs with comparable variant allele frequencies. Turnaround time of NGS results was 1 day for SN compared to 4-10 days for CB. CONCLUSIONS: We were able to demonstrate the usefulness of SN for reliable rapid molecular results. We successfully incorporated the workflow for tissue handling and processing among our clinical, cytopathology, and molecular teams. Molecular results were available at the same time as the cytologic diagnosis, allowing for timely reporting of a comprehensive diagnosis. This approach is particularly useful in patients with advanced disease requiring urgent management.


Assuntos
Broncoscopia , Carcinoma Pulmonar de Células não Pequenas , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico , Sequenciamento de Nucleotídeos em Larga Escala , Neoplasias Pulmonares , Humanos , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico/métodos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Broncoscopia/métodos , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Mutação , Fluxo de Trabalho
16.
Int J Surg Case Rep ; 118: 109621, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38636161

RESUMO

INTRODUCTION AND IMPORTANCE: It is estimated that 1 out of 5 patients with cancer will experience bone metastasis. With non-small cell lung cancer by itself having 220.000 reported cases per year, but the prevalence of soft tissue metastasis from lung cancer is only 2.3 % making it commonly overlooked as a possible metastasis site. CASE PRESENTATION: Male presents with a lump and pain on the right upper arm. A 8 cm × 8 cm mass was palpated under the biceps. CT-scan showed a lung lesion on the anterior segment. Shoulder MRI showed a dense, lobulated, and indefinitely demarcated soft tissue mass approximately 5.6 cm × 7.8 cm × 8.8 cm. The patient was treated with wide excision of the tumor. Core biopsy showed a metastatic adenosquamous carcinoma with suspected primary lesion from the respiratory tract. Treatment with targeted chemotherapy and radiotherapy were then done to the patient. The patient was discharged without any complications and is still at remission at the 6 months post-operative checkup. CLINICAL DISCUSSION: Soft tissue metastasis of lung cancer cell is a rare but a very real phenomenon. In our case the diagnosis of the soft tissue mass as a metastasis from the lungs was decided on a clinical, physical, radiological, and histological basis without using immunohistochemistry. CONCLUSION: MRI, biopsy, and immunohistochemistry are traditionally needed to confirm the diagnosis but in select cases, radiological and microscopic examinations along with clinical correlation are enough to ascertain the diagnosis. While it is rare, a soft tissue metastasis should always be suspected in lung cancer patients that have a palpable mass.

17.
Cureus ; 16(3): e56113, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38618349

RESUMO

We report an interesting case of skeletal muscle metastasis from lung cancer. Skeletal muscle metastasis is an unusual clinical occurrence and therefore lacks a standardized treatment approach. A 60-year-old female patient initially presented with abdominal pain and was found to have right lung consolidation, two hepatic lesions, and a lesion to the sartorius muscle. Initially treated as pneumonia, questions arose as to the lesion to the liver as well as the sartorius muscle. The primary site of malignancy was initially questioned due to the large size of the two hepatic lesions, with differential diagnoses including lung or hepatic origin. The sartorius muscle biopsy confirmed the presence of an adenocarcinoma lesion, consistent with non-small cell lung cancer (NSCLC).

18.
Int Cancer Conf J ; 13(3): 218-222, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38962041

RESUMO

Immune checkpoint inhibitors (ICIs) are the current standard of care for non-small-cell lung cancer (NSCLC). Myocarditis is a rare but serious immune-related adverse event (irAE) associated with ICI therapy. We present a patient who received a single dose of pembrolizumab for NSCLC and developed ICI-associated pneumonia. Although pneumonia improved with corticosteroid therapy, the patient subsequently developed ICI-associated fulminant myocarditis. Despite high-dose corticosteroid therapy, the patient died on day 30 after pembrolizumab initiation. Even if an observed irAE was effectively treated, clinicians should remain vigilant for other irAEs, especially those that are difficult to control with low-dose corticosteroids.

19.
Cureus ; 15(4): e38319, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37261190

RESUMO

Primary lung carcinoma with distant metastasis is a life-threatening diagnosis that presents many unique challenges due to the severity of the disease at the time of presentation. We investigated a life-threatening primary lung carcinoma with distant metastasis in a 73-year-old transgender woman, which posed unique challenges due to the advanced stage of the disease at presentation. The patient exhibited nonspecific musculoskeletal and neurological symptoms resulting from the primary lung carcinoma metastasizing to her liver, bones, and brain. We evaluated various imaging modalities that aided in determining the disease's severity and identifying complications related to metastasis. Although these efforts can offer symptomatic relief, the overall prognosis remains poor when metastasis spreads to multiple organs, particularly the brain, as remission may no longer be attainable.

20.
Cancers (Basel) ; 15(14)2023 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-37509399

RESUMO

Microwave thermal ablation is a promising emerging treatment for early-stage lung cancer. Applicator design optimisation and treatment planning rely on accurate knowledge of dielectric tissue properties. Limited dielectric data are available in the literature for human lung tissue and pulmonary tumours. In this work, neoplastic and non-neoplastic lung dielectric properties are characterised and correlated with gross and histological morphology. Fifty-six surgical specimens were obtained from twelve patients undergoing lung resection for lung cancer in University Hospital of Galway, Ireland. Dielectric spectroscopy in the microwave frequency range (500 MHz-8.5 GHz) was performed on the ex vivo lung specimens with the open-ended coaxial probe technique (in the Department of Pathology). Dielectric data were analysed and correlated with the tissue histology. The dielectric properties of twelve lung tumours (67% non-small cell carcinoma (NSCC)) and uninvolved lung parenchyma were obtained. The values obtained from the neoplastic lung specimens (relative permittivity: 52.0 ± 5.4, effective conductivity: 1.9 ± 0.2 S/m, at 2.45 GHz) were on average twice the value of the non-neoplastic lung specimens (relative permittivity: 28.3 ± 6.7, effective conductivity: 1.0 ± 0.3 S/m, at 2.45 GHz). Dense fibrosis was comparable with tumour tissue (relative permittivity 49.3 ± 4.6, effective conductivity: 1.8 ± 0.1 S/m, at 2.45 GHz).

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