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1.
Curr Opin Pulm Med ; 30(1): 35-47, 2024 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-37916619

RESUMO

PURPOSE OF REVIEW: Technological advancement in low-dose computed tomography resulted in an increased incidental discovery of early-stage lung cancer and multifocal ground glass opacity. The demand for parenchyma-preserving treatment strategies is greater now than ever. Pulmonary ablative therapy is a groundbreaking technique to offer local ablative treatment in a lung-sparing manner. It has become a promising technique in lung cancer management with its diverse applicability. In this article, we will review the current development of ablative therapy in lung and look into the future of this innovative technique. RECENT FINDINGS: Current literature suggests that ablative therapy offers comparable local disease control to other local therapies and stereotactic body radiation therapy (SBRT), with a low risk of complications. In particular, bronchoscopic microwave ablation (BMWA) has considerably fewer pleural-based complications due to the avoidance of pleural puncture. BMWA can be considered in the multidisciplinary treatment pathway as it allows re-ablation and allows SBRT after BMWA. SUMMARY: With the benefits which ablative therapy offers and its ability to incorporate into the multidisciplinary management pathway, we foresee ablative therapy, especially BMWA gaining significance in lung cancer treatment. Future directions on developing novel automated navigation platforms and the latest form of ablative energy would further enhance clinical outcomes for our patients.


Assuntos
Neoplasias Pulmonares , Radiocirurgia , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/cirurgia , Pulmão/patologia , Tomografia Computadorizada por Raios X
2.
Ann Surg ; 275(3): e600-e602, 2022 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-34596079

RESUMO

INTRODUCTION: Use of neoadjuvant immunotherapy agent in advanced stage NSCLC is controversial. Herein, we aim to report on a case series of successful conversion from initial unresectable stage cIIIB NSCLC to radical minimally invasive surgery through immunochemotherapy; with particular attention given to surgical outcomes and survival benefit of surgery. METHODS: Fifty-one patients with initial stage cIIIB NSCLC who received PD-1 agents plus platinum-based chemotherapy between May, 2018 to August, 2020 were retrospectively identified. Surgical and oncological outcomes of enrolled patients were collected. RESULTS: Of 31 patients who underwent subsequent resection, 23 (74.2%) patients underwent lobectomy, 1 (3.2%) underwent pneumonectomy, 5 (16.1%) underwent sleeve lobectomy, and 2 (6.5%) with bilobectomy. The median surgical time was 205 minutes (range, 100-520). The average blood loss was 185 (range: 10-1100) ml. Dense adhesions or fibrosis was noted in 15 cases. The median postoperative hospital stay was 6 (range: 3-13) days. No surgical-related mortality was recorded, only 5 patients (16.1%) experienced any postoperative morbidity (no grade 3 complications). Ten patients (32.3%) had major pathological response, with mediastinal down-staging been observed in 22/31 (71.0%) patients. With a median after up of 15.4 months, thirty-one patients that had surgery had relatively longer median DFS/PFS compared to that of either non-responders or responders that without surgery (27.5 vs. 4.7 vs. 16.7 months, respectively). CONCLUSIONS: Radical surgery after chemoimmunotherapy in initial unresectable stage IIIB NSCLC seems to be safe with low surgical-related mortality and morbidity, and was favorably associated with longer DFS/PFS compared to those without surgery.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/cirurgia , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Terapia Combinada , Humanos , Imunoterapia , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Procedimentos Cirúrgicos Minimamente Invasivos , Estadiamento de Neoplasias , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento
3.
Thorac Cardiovasc Surg ; 68(3): 253-255, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-30634186

RESUMO

Small pulmonary lesions can be difficult to localize during video-assisted thoracoscopic surgery. Electromagnetic navigation bronchoscopy (ENB) dye marking of the lesion, particularly when guided by cone beam computed tomography in the hybrid operating room (HOR), is an emerging approach. However, issues with confirmation of dye injection and intraoperative visualization of the colored dye can be unpredictable and challenging. To address these uncertainties, we present our technique of ENB dye marking localization of lung nodule using the triple-contrast dye method in the HOR.


Assuntos
Broncoscopia , Corantes/administração & dosagem , Meios de Contraste/administração & dosagem , Fenômenos Eletromagnéticos , Verde de Indocianina/administração & dosagem , Iohexol/administração & dosagem , Neoplasias Pulmonares/diagnóstico por imagem , Azul de Metileno/administração & dosagem , Nódulo Pulmonar Solitário/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Humanos , Injeções Intralesionais , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Pneumonectomia , Valor Preditivo dos Testes , Nódulo Pulmonar Solitário/patologia , Nódulo Pulmonar Solitário/cirurgia , Cirurgia Assistida por Computador , Cirurgia Torácica Vídeoassistida , Carga Tumoral
4.
Oncologist ; 24(10): 1368-1374, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-30872465

RESUMO

BACKGROUND: The efficacy of adjuvant targeted therapy for operable lung cancer is still under debate. Comprehensive genetic profiling is needed for detecting co-mutations in resected epidermal growth factor receptor (EGFR)-mutated lung adenocarcinoma (ADC), which may interfere the efficacy of adjuvant tyrosine kinase inhibitor (TKI) treatment. MATERIALS AND METHODS: Mutation profiling of 416 cancer-relevant genes was conducted for 139 resected stage I-IIIa lung ADCs with EGFR mutations using targeted next-generation sequencing. Co-mutation profiles were systematically analyzed. RESULTS: Rare EGFR alterations other than exon 19 deletion and L858R, such as L861Q (∼3%) and G719A (∼2%), were identified at low frequencies. Approximately 10% of patients had mutations in EGFR exon 20 that could confer resistance to first-generation TKIs. Ninety-one percent of patients harbored at least one co-mutation in addition to the major EGFR mutation. TP53 was the top mutated gene and was found more frequently mutated at later stage. Markedly, NF1 mutations were found only in stage II-III ADCs. Conversely, RB1 mutations were more frequent in stage I ADCs, whereas APC mutations were observed exclusively in this group. Thirty-four percent of patients with EGFR TKI-sensitizing mutations had genetic alterations involving EGFR downstream effectors or bypass pathways that could affect the response to EGFR TKIs, such as PIK3CA, BRCA1, and NOTCH1. CONCLUSION: Operable lung ADCs with EGFR TKI-sensitizing mutations are associated with a high proportion of co-mutations. Mutation profiling of these resected tumors could facilitate in determining the applicability and efficacy of adjuvant EGFR TKI therapeutic strategy. IMPLICATIONS FOR PRACTICE: The efficacy of adjuvant epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) therapy for lung cancer harboring EGFR mutation after surgical resection is still under debate. Next-generation sequencing of 416 cancer-relevant genes in 139 resected lung cancers revealed the co-mutational landscape with background EGFR mutation. Notably, the study identified potential EGFR TKI-resistant mutations in 34.71% of patients with a drug-sensitizing EGFR mutation and who were naive in terms of targeted therapy. A comprehensive mutation profiling of these resected tumors could facilitate in determining the applicability and efficacy of adjuvant EGFR TKI therapeutic strategy for these patients.


Assuntos
Adenocarcinoma/genética , Genômica/métodos , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Neoplasias Pulmonares/genética , Adenocarcinoma/patologia , Receptores ErbB/genética , Feminino , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Mutação
5.
Ann Surg Oncol ; 26(7): 2053-2062, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30900105

RESUMO

BACKGROUND: Models for predicting the survival outcomes of stage I non-small-cell lung cancer (NSCLC) defined by the newly released 8th edition TNM staging system are scarce. This study aimed to develop a nomogram for predicting the cancer-specific survival (CSS) of these patients and identifying individuals with a higher risk for CSS. METHODS: A total of 30,475 NSCLC cases were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. We identified and integrated the risk factors to build a nomogram. The model was subjected to bootstrap internal validation with the SEER database, and external validation with a multicenter cohort of 1133 patients from China. The difference in the impact of adjuvant chemotherapy on model-defined high- and low-risk patients was examined using the National Cancer Database (NCDB). RESULTS: Eight independent prognostic factors were identified and integrated into the model. The calibration curves showed good agreement. The concordance index (C-index) of the nomogram was higher than that of the staging system (IA1, IA2, IA3, and IB) (internal validation set 0.63 vs. 0.56; external validation set 0.66 vs. 0.55; both p < 0.01). Specifically, 21.7% of stage IB patients (7.5% of all stage I) were categorized into the high-risk group (score > 30). There was a significant interaction effect between the adjuvant chemotherapy and risk groups in the NCDB cohort (p = 0.003). CONCLUSIONS: We established a practical nomogram to predict CSS for 8th edition stage I NSCLC. A prospective study is warranted to determine its role in identifying adjuvant chemotherapy candidates.


Assuntos
Adenocarcinoma Bronquioloalveolar/mortalidade , Adenocarcinoma/mortalidade , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma de Células Escamosas/mortalidade , Neoplasias Pulmonares/mortalidade , Estadiamento de Neoplasias/normas , Nomogramas , Adenocarcinoma/patologia , Adenocarcinoma/terapia , Adenocarcinoma Bronquioloalveolar/patologia , Adenocarcinoma Bronquioloalveolar/terapia , Idoso , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/terapia , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/terapia , Estudos de Coortes , Terapia Combinada , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/terapia , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Programa de SEER , Taxa de Sobrevida
6.
Mod Pathol ; 31(9): 1381-1390, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29713040

RESUMO

Immune checkpoint blockade targeting the PD-1/PD-L1 axis has recently demonstrated efficacy and promise in cancer treatment. Appropriate biomarker selection is therefore essential for improving treatment efficacy. However, the establishment of PD-L1 assay in pathology laboratories is complicated by the presence of multiple testing platforms using different scoring systems. Here we assessed the PD-L1 expression in 713 consecutive non-small cell lung carcinomas by four commercially available PD-L1 immunohistochemical assays, namely, 22C3, 28-8, SP142 and SP263. The analytical performances of the four assays and diagnostic performances across clinically relevant cutoffs were evaluated. The prevalence of PD-L1 (22C3) expression was 21% with a ≥50% cutoff and 56% with a ≥1% cutoff. High PD-L1 expression (using a ≥50% cutoff) was significantly associated with male sex (P = 0.001), ever smoking history (P < 0.001), squamous cell carcinoma (P = 0.001), large cell carcinoma (P < 0.001), lymphoepithelioma-like carcinoma (P = 0.006), sarcomatoid carcinoma (P < 0.001), mutant KRAS (P = 0.005) and wild-type EGFR (P = 0.003). Elevated PD-L1 expression was also significantly associated with shorter survival in patients with adenocarcinoma (log-rank P = 0.026) and remained an independent prognostic factor by multivariable analysis. Among the four assays, 22C3, 28-8 and SP263 were highly concordant for tumor cell scoring. With a cutoff of ≥50% (i.e., the threshold for first-line patient selection), inter-rater agreement was high among the three assays with percentage agreement >97%. In conclusion, three PD-L1 assays showed good analytical performance and a high agreement with each other, but not all cases were correctly classified using the same clinical cutoff. Further studies comparing the predictive value of these assays are required to address the interchangeability of these assays for clinical use.


Assuntos
Antígeno B7-H1/metabolismo , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Neoplasias Pulmonares/metabolismo , Pulmão/metabolismo , Biomarcadores Tumorais , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Feminino , Humanos , Imuno-Histoquímica , Pulmão/patologia , Pulmão/cirurgia , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Prognóstico , Taxa de Sobrevida
7.
Mol Cancer ; 16(1): 124, 2017 07 17.
Artigo em Inglês | MEDLINE | ID: mdl-28716029

RESUMO

BACKGROUND: The role of cancer cell FOXP3 in tumorigenesis is conflicting. We aimed to study FOXP3 expression and regulation, function and clinical implication in human non-small cell lung cancer (NSCLC). METHODS: One hundred and six patients with histologically-confirmed NSCLC who underwent surgery were recruited for the study. Tumor samples and NSCLC cell lines were used to examine FOXP3 and its related molecules. Various cell functions related to tumorigenesis were performed. In vivo mouse tumor xenograft was used to confirm the in vitro results. RESULTS: NSCLC patients with the high level of FOXP3 had a significant decrease in overall survival and recurrence-free survival. FOXP3 overexpression significantly induced cell proliferation, migration, and invasion, whereas its inhibition impaired its oncogenic function. In vivo studies confirmed that FOXP3 promoted tumor growth and metastasis. The ectopic expression of FOXP3 induced epithelial-mesenchymal transition (EMT) with downregulation of E-cadherin and upregulation of N-cadherin, vimentin, snail, slug, and MMP9. The oncogenic effects by FOXP3 could be attributed to FOX3-mediated activation of Wnt/ß-catenin signaling, as FOXP3 increased luciferase activity of Topflash reporter and upregulated Wnt signaling target genes including c-Myc and Cyclin D1 in NSCLC cells. Co-immunoprecipitation results further indicated that FOXP3 could physically interacted with ß-catenin and TCF4 to enhance the functions of ß-catenin and TCF4, inducing transcription of Wnt target genes to promote cell proliferation, invasion and EMT induction. CONCLUSIONS: FOXP3 can act as a co-activator to facilitate the Wnt-b-catenin signaling pathway, inducing EMT and tumor growth and metastasis in NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Transição Epitelial-Mesenquimal , Fatores de Transcrição Forkhead/metabolismo , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Via de Sinalização Wnt , Animais , Carcinogênese/patologia , Linhagem Celular Tumoral , Proliferação de Células , Células HEK293 , Humanos , Camundongos Nus , Metástase Neoplásica , Prognóstico
8.
Thorac Cardiovasc Surg ; 64(4): 348-53, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25602850

RESUMO

Background Video-assisted thoracic surgery (VATS) for major lung resection has undergone major changes from three or four-port approach to the recently possible single-port VATS approach. Outcomes following single-port VATS major lung resection are analyzed to determine safety and efficacy. Methods A prospective database of 150 consecutive patients who underwent single-port VATS major lung resection between March 2012 and January 2014 was reviewed. Patient demographics, perioperative parameters, histopathology, and outcomes up to follow-up of 2 years were analyzed by descriptive and Kaplan-Meier survival statistics. Results Single-port VATS major lung resection was successfully performed in 142 patients (conversion rate 5.3%) for both malignant and benign diseases of the lung. Overall, 130 patients (87%) had nonsmall-cell lung carcinoma (NSCLC), 9 (6%) had other types of primary lung cancer, and the remaining for secondary malignancies and benign diseases. Among the 130 patients with NSCLC, 93 (71.5%) were stage I, 28 were stage II (21.5%), and 9 (7%) were stage III or greater. There was no intraoperative or 30-day mortality. However, one perioperative death occurred on day 49, and another on day 60 postoperatively due to infective causes. The overall 2-year mortality rate for all patients was 3%. The disease-free survival rate for subgroups, stage I NSCLC, and stage II or greater NSCLC were 96 and 83%, respectively. Conclusions Single-port VATS major lung resection for malignant and benign lung diseases is associated with low perioperative morbidity and mortality. Disease-free survival rates for NSCLC are acceptable and comparable with conventional VATS.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/cirurgia , Neoplasias Pulmonares/cirurgia , Pneumonectomia/métodos , Cirurgia Torácica Vídeoassistida , Idoso , Perda Sanguínea Cirúrgica , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Bases de Dados Factuais , Intervalo Livre de Doença , Feminino , Hong Kong , Hospitais Universitários , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Duração da Cirurgia , Pneumonectomia/efeitos adversos , Pneumonectomia/mortalidade , Complicações Pós-Operatórias/etiologia , Fatores de Risco , Seul , Cirurgia Torácica Vídeoassistida/efeitos adversos , Cirurgia Torácica Vídeoassistida/mortalidade , Fatores de Tempo , Resultado do Tratamento
9.
Cancer ; 121 Suppl 17: 3130-45, 2015 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-26331820

RESUMO

BACKGROUND: Previous studies have shown that the levels of 15-lipoxygenase 1 (15-LOX-1) and 15-LOX-2 as well as their metabolites 13-S-hydroxyoctadecadienoic acid (13(S)-HODE) and 15(S)-hydroxyeicosatetraenoic acid (15(S)-HETE) are significantly reduced in smokers with non-small cell lung carcinoma (NSCLC). Furthermore, animal model experiments have indicated that the reduction of these molecules occurs before the establishment of cigarette smoking carcinogen-induced lung tumors, and this suggests roles in lung tumorigenesis. However, the functions of these molecules remain unknown in NSCLC. METHODS: NSCLC cells were treated with exogenous 13(S)-HODE and 15(S)-HETE, and then the ways in which they affected cell function were examined. 15-LOX-1 and 15-LOX-2 were also overexpressed in tumor cells to restore these 2 enzymes to generate endogenous 13(S)-HODE and 15(S)-HETE before cell function was assessed. RESULTS: The application of exogenous 13(S)-HODE and 15(S)-HETE significantly enhanced the activity of peroxisome proliferator-activated receptor γ (PPARγ), inhibited cell proliferation, induced apoptosis, and activated caspases 9 and 3. The overexpression of 15-LOX-1 and 15-LOX-2 obviously promoted the endogenous levels of 13(S)-HODE and 15(S)-HETE, which were demonstrated to be more effective in the inhibition of NSCLC. CONCLUSIONS: This study has demonstrated that exogenous or endogenous 13(S)-HODE and 15(S)-HETE can functionally inhibit NSCLC, likely by activating PPARγ. The restoration of 15-LOX activity to increase the production of endogenous 15(S)-HETE and 13(S)-HODE may offer a novel research direction for molecular targeting treatment of smoking-related NSCLC. This strategy can potentially avoid side effects associated with the application of synthetic PPARγ ligands.


Assuntos
Araquidonato 15-Lipoxigenase/biossíntese , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Ácidos Graxos Insaturados/administração & dosagem , Ácidos Hidroxieicosatetraenoicos/administração & dosagem , Antineoplásicos/administração & dosagem , Apoptose/efeitos dos fármacos , Araquidonato 15-Lipoxigenase/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , PPAR gama/genética
10.
Am J Emerg Med ; 33(10): 1501-4, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26184524

RESUMO

Traditional transfusion guidelines suggest that fresh frozen plasma (FFP) should be given based on laboratory or clinical evidence of coagulopathy or acute loss of 1 blood volume. This approach tends to result in a significant lag time between the first units of erythrocytes and FFP in trauma requiring massive transfusion. In severe trauma, observational studies have found an association between increased survival and aggressive use of FFP and platelets such that FFP:platelet:erythrocyte ratio approaches 1:1:1 to 2 from the first units of erythrocytes given. There are considerable concerns over either approach, and no randomized controlled trials have been published comparing the 2 approaches. Nowadays, trauma clinicans are incorporating the strenghts of both approaches and are no longer treating them as a dichotomy. Specifically, "1:1:1" proponents have devised 1:1:1 activation criteria to minimize unnecessary FFP and platelet transfusion and are prepared to deactivate the protocol as soon as patient is stabilized. Similarly, 1:1:1 skeptics are more mindful of the need to be proactive about trauma coagulopathy and the inherent delays in FFP administration in trauma patients.


Assuntos
Transfusão de Componentes Sanguíneos/métodos , Transfusão de Componentes Sanguíneos/normas , Protocolos Clínicos/normas , Hemorragia/terapia , Ferimentos e Lesões/complicações , Serviço Hospitalar de Emergência , Transfusão de Eritrócitos , Humanos , Plasma , Transfusão de Plaquetas
11.
J Bronchology Interv Pulmonol ; 31(2): 165-174, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-37747275

RESUMO

BACKGROUND: Image-guided thermal ablation is a minimally invasive local therapy for lung malignancies. NAVABLATE characterized the safety and performance of transbronchial microwave ablation (MWA) in the lung. METHODS: The prospective, single-arm, 2-center NAVABLATE study (NCT03569111) evaluated transbronchial MWA in patients with histologically confirmed lung malignancies ≤30 mm in maximum diameter who were not candidates for, or who declined, both surgery and stereotactic body radiation therapy. Ablation of 1 nodule was allowed per subject. The nodule was reached with electromagnetic navigation bronchoscopy. Cone-beam computed tomography was used to verify the ablation catheter position and to evaluate the ablation zone postprocedure. The primary end point was composite adverse events related to the transbronchial MWA device through 1-month follow-up. Secondary end points included technical success (nodule reached and ablated according to the study protocol) and technique efficacy (satisfactory ablation based on 1-month follow-up imaging). RESULTS: Thirty subjects (30 nodules; 66.7% primary lung, 33.3% oligometastatic) were enrolled from February 2019 to September 2020. The pre-procedure median nodule size was 12.5 mm (range 5 to 27 mm). Procedure-day technical success was 100% (30/30), with a mean ablative margin of 9.9±2.7 mm. One-month imaging showed 100% (30/30) technique efficacy. The composite adverse event rate related to the transbronchial MWA device through 1-month follow-up was 3.3% (1 subject, mild hemoptysis). No deaths or pneumothoraces occurred. Four subjects (13.3%) experienced grade 3 complications; none had grade 4 or 5. CONCLUSION: Transbronchial microwave ablation is an alternative treatment modality for malignant lung nodules ≤30 mm. There were no deaths or pneumothorax. In all, 13.3% of patients developed grade 3 or above complications.


Assuntos
Ablação por Cateter , Neoplasias Pulmonares , Humanos , Ablação por Cateter/efeitos adversos , Ablação por Cateter/métodos , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/cirurgia , Neoplasias Pulmonares/patologia , Micro-Ondas/uso terapêutico , Pneumotórax/etiologia , Estudos Prospectivos , Resultado do Tratamento
12.
Int J Surg ; 110(1): 238-252, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-37755384

RESUMO

BACKGROUND: Lymph node (LN) dissection is a common procedure for non-small cell lung cancer (NSCLC) to ascertain disease severity and treatment options. However, murine studies have indicated that excising tumor-draining LNs diminished immunotherapy effectiveness, though its applicability to clinical patients remains uncertain. Hence, the authors aim to illustrate the immunological implications of LN dissection by analyzing the impact of dissected LN (DLN) count on immunotherapy efficacy, and to propose a novel 'immunotherapy-driven' LN dissection strategy. MATERIALS AND METHODS: The authors conducted a retrospective analysis of NSCLC patients underwent anti-PD-1 immunotherapy for recurrence between 2018 and 2020, assessing outcomes based on DLN count stratification. RESULTS: A total of 144 patients were included, of whom 59 had a DLN count less than or equal to 16 (median, IQR: 11, 7-13); 66 had a DLN count greater than 16 (median, IQR: 23, 19-29). With a median follow-up time of 14.3 months (95% CI: 11.0-17.6), the overall median progression-free survival (PFS) was 7.9 (95% CI: 4.1-11.7) months, 11.7 (95% CI: 7.9-15.6) months in the combination therapy subgroup, and 4.8 (95% CI: 3.1-6.4) months in the immunotherapy alone subgroup, respectively. In multivariable Cox analysis, DLN count less than or equal to 16 is associated with an improved PFS in all cohorts [primary cohort: HR=0.26 (95% CI: 0.07-0.89), P =0.03]; [validation cohort: HR=0.46 (95% CI: 0.22-0.96), P =0.04]; [entire cohort: HR=0.53 (95% CI: 0.32-0.89), P =0.02]. The prognostic benefit of DLN count less than or equal to 16 was more significant in immunotherapy alone, no adjuvant treatment, pN1, female, and squamous carcinoma subgroups. A higher level of CD8+ central memory T cell (Tcm) within LNs was associated with improved PFS (HR: 0.235, 95% CI: 0.065-0.845, P =0.027). CONCLUSIONS: An elevated DLN count (cutoff: 16) was associated with poorer immunotherapy efficacy in recurrent NSCLC, especially pronounced in the immunotherapy alone subgroup. CD8+Tcm proportions in LNs may also impact immunotherapy efficacy. Therefore, for patients planned for adjuvant immunotherapy, a precise rather than expanded lymphadenectomy strategy to preserve immune-depending LNs is recommended.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Feminino , Animais , Camundongos , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Neoplasias Pulmonares/cirurgia , Estudos Retrospectivos , Recidiva Local de Neoplasia/cirurgia , Excisão de Linfonodo , Imunoterapia
13.
Pharmacol Ther ; 241: 108333, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36528259

RESUMO

Although in the last few decades we have witnessed the rapid development of treatments for non-small cell lung cancer (NSCLC), it still remains the leading cause of cancer-related death. Increasing efforts have been devoted to exploring potential biomarkers and molecular targets for NSCLC. Foxp3, a transcription factor that was discovered as a master regulator of regulatory T cells (Tregs), has been found to express abnormally in tumoral cells including lung cancer cells. In recent years, increasing evidence have surfaced, revealing the carcinogenic effect of FOXP3 in lung cancer. In this review, we analyzed and summarized the function of FOXP3, its regulation and therapeutic potentials in NSCLC, with a hope to facilitate the development of novel treatments for NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/metabolismo , Fatores de Transcrição Forkhead , Pulmão/metabolismo , Linfócitos T Reguladores
14.
AME Case Rep ; 7: 13, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37122960

RESUMO

Background: Transbronchial ablation of lung nodules is gaining popularity as part of lung-preserving strategy for patients with multifocal lung cancers or multiple lung oligometastases. Accuracy in placement of ablation catheter is of utmost importance in order to achieve adequate ablation margin. However, older systems are not precise enough for confident placement of ablation catheter and often require multiple cone-beam CT (CBCT) to confirm and readjust its position. The following case is the first microwave lung ablation utilizing the novel IllumisiteTM platform (Medtronic, Minneapolis, MN, USA) in the hybrid operating room (HOR), with enhanced accuracy and workflow. Case Description: A 66-year-old lady had multiple resected adenocarcinomas in bilateral lungs. Upon CT monitoring a right middle lobe (RML) ground glass opacity with solid centre was found to be suspicious due to increasing size and density. Transbronchial electromagnetic navigation bronchoscopy (ENB) microwave ablation of the lesion was performed as part of lung-conserving strategy. After initial navigation, the adjusted nodule position provided by the IllumisiteTM platform after correcting the CT-to-body divergence prompted operators to renavigate and readjust the position of the locatable guide (LG) swiftly to gain accurate access to the nodule, which was confirmed by CBCT. Positional data at the tip of extended working channel (EWC) also allowed precise placement of needle for subsequent ablation. Conclusions: IllumisiteTM is a novel electromagnetic navigational platform that corrects for CT-to-body divergence and ensures continuous locational information by an additional positional coil in the tip of EWC. This precision is especially important for the placement of ablation catheter, as slight deviation would lead to insufficient ablation margin and future recurrence. Workflow is improved by reducing the number of CBCT required for instrument position adjustment.

15.
Cancers (Basel) ; 15(4)2023 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-36831411

RESUMO

The demand for parenchyma-sparing local therapies for lung cancer is rising owing to an increasing incidence of multifocal lung cancers and patients who are unfit for surgery. With the latest evidence of the efficacy of lung cancer screening, more premalignant or early-stage lung cancers are being discovered and the paradigm has shifted from treatment to prevention. Transbronchial therapy is an important armamentarium in the local treatment of lung cancers, with microwave ablation being the most promising based on early to midterm results. Adjuncts to improve transbronchial ablation efficiency and accuracy include mobile C-arm platforms, software to correct for the CT-to-body divergence, metal-containing nanoparticles, and robotic bronchoscopy. Other forms of energy including steam vapor therapy and pulse electric field are under intensive investigation.

16.
Front Oncol ; 13: 1330468, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38322280

RESUMO

Introduction: Osimertinib is recommended by major guidelines for use in the adjuvant setting in patients with EGFR mutation-positive NSCLC following the significant improvement in disease-free survival observed in the Phase III ADAURA trials. Due to limited real-world data in the adjuvant setting, little guidance exists on how to approach potential recurrences either during or after the completion of the treatment. This study aimed to reach a broad consensus on key treatment decision criteria in the events of recurrence. Methods: To reach a broad consensus, a modified Delphi panel study was conducted consisting of two rounds of surveys, followed by two consensus meetings and a final offline review of key statements. An international panel of experts in the field of NSCLC (n=12) was used to provide clinical insights regarding patient management at various stages of NSCLC disease including patient monitoring, diagnostics, and treatment approach for specific recurrence scenarios. This study tested recurrences occurring 1) within or outside the central nervous system (CNS), 2) during or after the adjuvant-osimertinib regimen in NSCLC disease which is 3) amenable or not amenable to local consolidative therapy. Results: Panellists agreed on various aspects of patient monitoring and diagnostics including the use of standard techniques (e.g., CT, MRI) and tumour biomarker assessment using tissue and liquid biopsies. Consensus was reached on 6 statements describing treatment considerations for the specific NSCLC recurrence scenarios. Panellists agreed on the value of osimertinib as a monotherapy or as part of the overall treatment strategy within the probed recurrence scenarios and acknowledged that more clinical evidence is required before precise recommendations for specific patient populations can be made. Discussion: This study provides a qualitative expert opinion framework for clinicians to consider within their treatment decision-making when faced with recurrence during or after adjuvant-osimertinib treatment.

17.
JTCVS Tech ; 22: 265-272, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38152171

RESUMO

Objectives: Transbronchial microwave ablation of lung nodules using electromagnetic navigation bronchoscopy is an emerging local therapy for lung oligometastases and multifocal lung cancers as part of a lung-preserving strategy. Concomitant ablation of multiple lung nodules in a single operating session may provide a one-stop solution. Methods: Between April 2019 and April 2023, 25 patients had 2 or more lung nodules ablated concomitantly in our hybrid operating room. Nodules were proven or highly suspicious of malignancies or metastases. Feasibility and safety were retrospectively reviewed. Results: A total of 56 nodules in 25 patients received concomitant multi-nodular ablation. The mean age of patients was 60 years, and the reasons for the lung-preserving strategy were multifocal lung cancers (80%) and lung oligometastases (20%). Among those with multifocal disease, 65% had previous major lung resection for lung cancer. Two to 4 nodules were ablated in each session. The mean nodule size was 9.9 mm (range, 5-20 mm), and the mean minimal margin was 5.9 mm. When comparing concomitant nodule ablation with the 103 single-nodule ablations performed in our institute, a mean of 86 minutes of operative time and 131 minutes of anesthetic time were saved. There were no increased complications despite overlapping ablation zones, and the mean hospital stay was 1.23 days. The rate of pneumothorax was 8%, and that of pleural effusion, pain, and fever was 4% respectively. Conclusions: Concomitant transbronchial microwave ablation of multiple lung nodules is feasible, safe, and associated with reduction in overall anesthetic and operative time. It is an important armamentarium in the contemporary lung-preserving strategy for battling multifocal lung cancers or lung oligometastases.

18.
Gland Surg ; 12(6): 749-766, 2023 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-37441012

RESUMO

Background: Surgical technique plays an essential role in achieving good health outcomes. However, the quality of surgical technique reporting remains heterogeneous. Reporting checklists could help authors to describe the surgical technique more transparently and effectively, as well as to assist reviewers and editors evaluate it more informatively, and promote readers to better understand the technique. We previously developed SUPER (surgical technique reporting checklist and standards) to assist authors in reporting their research that contains surgical technique more transparently. However, further explanation and elaboration of each item are needed for better understanding and reporting practice. Methods: We searched surgical literature in PubMed, Google Scholar and journal websites published up to January 2023 to find multidiscipline examples in various article types for each SUPER item. Results: We explain the 22 items of the SUPER and provide rationales item by item alongside. We provide 69 examples from 53 literature that present optimal reporting of the 22 items. Article types of examples include pure surgical technique, and case reports, observational studies and clinical trials that contain surgical technique. Examples are multidisciplinary, including general surgery, orthopaedical surgery, cardiac surgery, thoracic surgery, gastrointestinal surgery, neurological surgery, oncogenic surgery, and emergency surgery etc. Conclusions: Along with SUPER article, this explanation and elaboration file can promote deeper understanding on the SUPER items. We hope that the article could further guide surgeons and researchers in reporting, and assist editors and peer reviewers in reviewing manuscripts related to surgical technique.

19.
J Clin Epidemiol ; 155: 1-12, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36574532

RESUMO

OBJECTIVES: To identify reporting guidelines related to surgical technique and propose recommendations for areas that require improvement. STUDY DESIGN AND SETTING: A protocol-guided scoping review was conducted. A literature search of MEDLINE, the EQUATOR Network Library, Google Scholar, and Networked Digital Library of Theses and Dissertations was conducted to identify surgical technique reporting guidelines published up to December 31, 2021. RESULTS: We finally included 55 surgical technique reporting guidelines, vascular surgery (n = 18, 32.7%) was the most common among the clinical specialties covered. The included guidelines generally showed a low degree of international and multidisciplinary cooperation. Few guidelines provided a detailed development process (n = 14, 25.5%), conducted a systematic literature review (n = 13, 23.6%), used the Delphi method (n = 4, 7.3%), or described post-publication strategy (n = 6, 10.9%). The vast majority guidelines focused on the reporting of intraoperative period (n = 50, 90.9%). However, of the guidelines requiring detailed descriptions of surgical technique methodology (n = 43, 78.2%), most failed to provide guidance on what constitutes an adequate description. CONCLUSION: Our study demonstrates significant deficiencies in the development methodology and practicality of reporting guidelines for surgical technique. A standardized reporting guideline that is developed rigorously and focuses on details of surgical technique may serve as a necessary impetus for change.

20.
Hepatobiliary Surg Nutr ; 12(4): 534-544, 2023 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-37601001

RESUMO

Background: Existing reporting guidelines pay insufficient attention to the detail and comprehensiveness reporting of surgical technique. The Surgical techniqUe rePorting chEcklist and standaRds (SUPER) aims to address this gap by defining reporting standards for surgical technique. The SUPER guideline intends to apply to articles that encompass surgical technique in any study design, surgical discipline, and stage of surgical innovation. Methods: Following the EQUATOR (Enhancing the QUAlity and Transparency Of health Research) Network approach, 16 surgeons, journal editors, and methodologists reviewed existing reporting guidelines relating to surgical technique, reviewed papers from 15 top journals, and brainstormed to draft initial items for the SUPER. The initial items were revised through a three-round Delphi survey from 21 multidisciplinary Delphi panel experts from 13 countries and regions. The final SUPER items were formed after an online consensus meeting to resolve disagreements and a three-round wording refinement by all 16 SUPER working group members and five SUPER consultants. Results: The SUPER reporting guideline includes 22 items that are considered essential for good and informative surgical technique reporting. The items are divided into six sections: background, rationale, and objectives (items 1 to 5); preoperative preparations and requirements (items 6 to 9); surgical technique details (items 10 to 15); postoperative considerations and tasks (items 16 to 19); summary and prospect (items 20 and 21); and other information (item 22). Conclusions: The SUPER reporting guideline has the potential to guide detailed, comprehensive, and transparent surgical technique reporting for surgeons. It may also assist journal editors, peer reviewers, systematic reviewers, and guideline developers in the evaluation of surgical technique papers and help practitioners to better understand and reproduce surgical technique. Trial Registration: https://www.equator-network.org/library/reporting-guidelines-under-development/reporting-guidelines-under-development-for-other-study-designs/#SUPER.

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