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1.
Lung Cancer ; 191: 107558, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38569278

RESUMO

OBJECTIVES: Mediastinal neoplasms are typical but uncommon thoracic diseases with increasing incidence and unfavorable prognoses. A comprehensive understanding of their spatiotemporal distribution is essential for accurate diagnosis and timely treatment. However, previous studies are limited in scale and data coverage. Therefore, this study aims to elucidate the distribution of mediastinal lesions, offering valuable insights into this disease. MATERIALS AND METHODS: This multi-center, hospital-based observational study included 20 nationwide institutions. A retrospective search of electronic medical records from January 1st, 2009, to December 31st, 2020, was conducted, collecting sociodemographic data, computed tomography images, and pathologic diagnoses. Analysis focused on age, sex, time, location, and geographical region. Comparative assessments were made with global data from a multi-center database. RESULTS: Among 7,765 cases, thymomas (30.7%), benign mediastinal cysts (23.4%), and neurogenic tumors (10.0%) were predominant. Distribution varied across mediastinal compartments, with thymomas (39.6%), benign cysts (28.1%), and neurogenic tumors (51.9%) most prevalent in the prevascular, visceral, and paravertebral mediastinum, respectively. Age-specific variations were notable, with germ cell tumors prominent in patients under 18 and aged 18-29, while thymomas were more common in patients over 30. The composition of mediastinal lesions across different regions of China remained relatively consistent, but it differs from that of the global population. CONCLUSION: This study revealed significant heterogeneity in the spatiotemporal distribution of mediastinal neoplasms. These findings provide useful demographic data when considering the differential diagnosis of mediastinal lesions, and would be beneficial for tailoring disease prevention and control strategies.


Assuntos
Neoplasias do Mediastino , Humanos , Masculino , Feminino , Neoplasias do Mediastino/epidemiologia , Neoplasias do Mediastino/patologia , Neoplasias do Mediastino/diagnóstico , Neoplasias do Mediastino/diagnóstico por imagem , Adulto , Pessoa de Meia-Idade , Estudos Retrospectivos , Adolescente , Adulto Jovem , Idoso , Criança , Análise Espaço-Temporal , Pré-Escolar , Tomografia Computadorizada por Raios X , Incidência
2.
Thorac Cancer ; 14(32): 3240-3244, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37779217

RESUMO

Pulmonary polymorphic carcinoma (PPC) is a rare and poorly differentiated form of non-small cell lung cancer (NSCLC), accounting for just approximately 0.1% to 0.4% of all NSCLC cases. Historically, the conventional treatments for PPC have been linked to a grim prognosis. However, with the advent of immune checkpoint inhibitors (ICIs), including PD-1 inhibitors, for the management of NSCLC, our center has witnessed encouraging outcomes in two PPC patients who underwent PD-1 inhibitor therapy. The first patient was a 70-year-old male who initially came to our attention after the discovery of a lung mass during a routine physical examination. A lung biopsy confirmed the diagnosis of PPC, and further complications included brain metastasis. Surgical intervention was conducted for the brain metastases, while PD-1 inhibitor therapy was employed for the lung tumors. The second patient was a 60-year-old male who was admitted with a history of persistent coughing and hemoptysis, which led to the diagnosis of a left lung tumor. Subsequent postoperative pathology revealed pulmonary adenocarcinoma coexisting with PPC. However, 2 months later, distant metastases were detected during a follow-up examination. The patient encountered difficulty in tolerating the adverse effects of chemotherapy, prompting the initiation of PD-1 inhibitor treatment. Notably, both patients underwent one cycle of PD-1 inhibitor therapy without encountering significant adverse reactions, and their responses proved to be promising during re-examinations. These findings suggest that surgery combined with immunotherapy PD-1 inhibitor therapy may represent an effective approach for the treatment of PPC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Carcinoma , Neoplasias Pulmonares , Masculino , Humanos , Idoso , Pessoa de Meia-Idade , Neoplasias Pulmonares/patologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Pulmão/patologia , Antígeno B7-H1/metabolismo
3.
Thorac Cancer ; 14(20): 1932-1940, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37246469

RESUMO

BACKGROUND: The aim of the study was to investigate differences in HLA-I alleles between lung adenocarcinoma patients and healthy controls and determine their association with PD-L1 expression and tumor mutational burden (TMB) to understand the mechanism underlying lung adenocarcinoma susceptibility. METHODS: Differences in HLA allele frequencies between the two groups were analyzed in a case-control study. PD-L1 expression and TMB in lung adenocarcinoma patients were determined and their relationships with HLA-I were analyzed. RESULTS: The lung adenocarcinoma group showed significantly higher HLA-A*30:01 (p = 0.0067, odds ratio [OR], 1.834; 95% confidence interval [CI]: 1.176-2.860), B*13:02 (p = 0.0050, OR, 1.855; 95% CI: 1.217-2.829), and C*06:02 (p = 0.0260, OR, 1.478; 95% CI: 1.060-2.060) and significantly lower B*51:01 (p = 0.0290, OR, 0.6019; 95% CI: 0.3827-0.9467), and C*14:02 (p = 0.0255, OR, 0.5089; 95% CI: 0.2781-0.9312) than the control group. Haplotype analysis results showed that HLA-A*30:01-B*13:02 (p = 0.0100, OR, 1.909; 95% CI: 1.182-3.085), A*11:01-C*01:02 (p = 0.0056, OR, 1.909; 95% CI: 1.182-3.085), A*30:01-C*06:02 (p = 0.0111, OR, 1.846; 95% CI: 1.147-2.969), and B*13:02-C*06:02 (p = 0.0067, OR, 1.846; 95% CI: 1.147-2.969) frequencies significantly increased and B*51:01-C*14:02 (p = 0.0219, OR, 0.490; 95% CI: 0.263-0.914) frequency significantly decreased in lung adenocarcinoma patients. Three-locus haplotype analysis showed that HLA-A*30:01-B*13:02-C*06:02 frequency (p = 0.0100, OR, 1.909; 95% CI: 1.182-3.085) significantly increased in patients. CONCLUSION: HLA-A*30:01, B*13:02, and C*06:02 may be the susceptibility genes and HLA-B*51:01 and C*14:01 act as the resistance genes of lung adenocarcinoma. The changes in HLA-I allele frequencies had no association with PD-L1 expression and TMB among these patients.


Assuntos
Adenocarcinoma de Pulmão , Carcinoma Pulmonar de Células não Pequenas , Antígenos HLA-A , Neoplasias Pulmonares , Humanos , Adenocarcinoma de Pulmão/genética , Alelos , Antígeno B7-H1/metabolismo , Biomarcadores Tumorais/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Estudos de Casos e Controles , Antígenos HLA-A/genética , Imunoterapia/métodos , Neoplasias Pulmonares/patologia , Mutação
4.
Digestion ; 104(3): 222-232, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36646064

RESUMO

INTRODUCTION: MIR155HG has been found to play an important role in malignant tumors, but little research has been done on its association with esophageal cancer (ESCC). The aim of this study was to investigate the relationship between MIR155HG polymorphisms and ESCC susceptibility in the Chinese Han population. METHODS: 511 ESCC patients and 487 healthy controls were selected for this study. All subjects were genotyped using the Agena MassARRAY platform. We assessed the association between seven single nucleotide polymorphisms (SNPs) of the MIR155HG and ESCC risk by genetic model analysis. The false discovery rate (FDR) test and Bonferroni correction were usually used to detect false positives for the results. Meanwhile, the interaction between SNPs was analyzed by multifactor dimensionality reduction software to predict the ESCC risk. RESULTS: The C allele of rs4143370 and the A allele of rs34904192 in MIR155HG can increase the risk of ESCC (odds ratio (OR) = 1.33, p = 0.024; OR = 1.30, p = 0.013). Furthermore, rs4143370 and rs34904192 were associated with an increased risk of ESCC. Stratified analysis showed that MIR155HG SNPs (rs4143370 and rs34904192) significantly increased ESCC risk in males. MIR155HG SNPs (rs4143370, rs34904192, and rs928883) were also strongly associated with an increased risk of ESCC in people aged >64 years. In addition, haplotype analysis of the seven SNPs of the MIR155HG showed that the CC haplotype was associated with ESCC risk (OR = 1.34, p = 0.024). CONCLUSION: This study revealed that MIR155HG SNPs were associated with an increased risk of ESCC. The results provided clues for clarifying the role of MIR155HG in ESCC.


Assuntos
Neoplasias Esofágicas , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , Humanos , Masculino , Povo Asiático/genética , Estudos de Casos e Controles , China/epidemiologia , População do Leste Asiático , Neoplasias Esofágicas/epidemiologia , Neoplasias Esofágicas/genética , Genótipo , Fatores de Risco
5.
J Cardiothorac Surg ; 17(1): 329, 2022 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-36539826

RESUMO

BACKGROUND: Surgical resection is the most effective curative management of benign rib tumors and carries an excellent prognosis. Due to complex anatomy and narrow field, higher rib resection is technically demanding and requires extensive dissection. CASE PRESENTATION: We report a case of second rib tumor resection performed transthoracic under Da Vinci robot assistance. A 32-year-old male complained about increasing pain in the left anterior chest wall. After 3D reconstruction of CT, it showed a well-circumscribed fusiform lesion with a multi-component structure. Measured 17 × 6 × 4 cm and extended into the chest cavity to the depth below the pectoralis minor muscle. The patient underwent robotic-assisted trans-thoracic second rib resection. At four weeks of outpatient follow-up, the patient reported no pain and uncomplicated wound healing. CONCLUSION: This minimally invasive approach offers optimal visualization and tissue manipulation while dramatically decreasing the possibility of collateral damage, hence ensuring fast function recovery. To the best of our knowledge, these kinds of procedures are rarely reported in detail.


Assuntos
Neoplasias , Procedimentos Cirúrgicos Robóticos , Procedimentos Cirúrgicos Torácicos , Masculino , Humanos , Adulto , Procedimentos Cirúrgicos Robóticos/métodos , Prognóstico , Costelas/cirurgia
6.
Transl Lung Cancer Res ; 11(11): 2318-2331, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36519017

RESUMO

The use of the white-light thoracoscopy is hampered by the low contrast between oncologic margins and surrounding normal parenchyma. As a result, many patients with in situ or micro-infiltrating adenocarcinoma have to undergo lobectomy due to a lack of tactile and visual feedback in the resection of solitary pulmonary nodules. Near-infrared (NIR) guided indocyanine green (ICG) fluorescence imaging technique has been widely investigated due to its unique capability in addressing the current challenges; however, there is no special consensus on the evidence and recommendations for its preoperative and intraoperative applications. This manuscript will describe the development process of a consensus on ICG fluorescence-guided thoracoscopic resection of pulmonary lesions and make recommendations that can be applied in a greater number of centers. Specifically, an expert panel of thoracic surgeons and radiographers was formed. Based on the quality of evidence and strength of recommendations, the consensus was developed in conjunction with the Chinese Guidelines on Video-assisted Thoracoscopy, and the National Comprehensive Cancer Network (NCCN) guidelines on the management of pulmonary lesions. Each of the statements was discussed and agreed upon with a unanimous consensus amongst the panel. A total of 6 consensus statements were developed. Fluorescence-guided thoracoscopy has unique advantages in the visualization of pulmonary nodules, and recognition and resection of the anterior plane of the pulmonary segment. The expert panel agrees that fluorescence-guided thoracoscopic surgery has the potential to become a routine operation for the treatment of pulmonary lesions.

7.
J Cardiothorac Surg ; 17(1): 281, 2022 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-36333814

RESUMO

BACKGROUND: Thoracoscopic segmentectomy is a common surgical procedure in thoracic surgery today. However, identifying the intersegmental plane is difficult in the surgical process. Therefore, we evaluated the feasibility of the arterial ligation method for determining the intersegmental plane and compared the demarcation status with the intravenous indocyanine green (ICG). METHODS: We retrospectively reviewed the records of 35 patients with peripheral small lung nodules who underwent thoracoscopic segmentectomy between May and December 2020. First, the preoperative three-dimensional reconstruction was performed to distinguish the location of lung nodules and the anatomical structures of targeted segmental arteries, veins, and bronchi. Second, the targeted segmental arteries were ligated, and the intersegmental plane was determined by the inflation-deflation technique. The waiting time for the appearance of the inflation-deflation line was recorded. Thirdly, the intersegmental plane was identified again using the ICG fluorescence method. Finally, the consistency of the two intersegmental planes was evaluated. RESULTS: The intersegmental planes were successfully observed in all patients using the arterial ligation method. Thirty-four patients underwent segmentectomy as planned, and one patient finally underwent lobectomy due to insufficient surgical margin. The waiting time for the appearance of the intersegmental plane by arterial ligation method was 13.7 ± 3.2 min (6-19 min). The intersegmental planes determined by the arterial ligation method and the ICG fluorescence method were comparable, with a maximum distance of no more than 5 mm between the two planes. The mean operative duration was 119.1 ± 34.9 min, and the mean blood loss was 76.9 ± 70.3 ml. No evident air leakage was found during the operation. Only one patient experienced a prolonged air leak (≥ 5 days) during the postoperative recovery. No atelectasis occurred in all cases. The chest tube duration was 3.1 ± 0.9 days. CONCLUSION: The arterial ligation method can efficiently and accurately identify the intersegmental plane, comparable to the ICG fluorescence method.


Assuntos
Neoplasias Pulmonares , Pneumonectomia , Humanos , Pneumonectomia/métodos , Neoplasias Pulmonares/cirurgia , Estudos Retrospectivos , Verde de Indocianina , Tubos Torácicos
9.
Sci Rep ; 12(1): 9979, 2022 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-35705647

RESUMO

Many methods are used to locate preoperative small pulmonary nodules. However, deficiencies of complications and success rates exist. We introduce a novel magnetic gel for small pulmonary nodules localization in rabbit model, and furtherly evaluate its safety and feasibility. Rabbits were used as the experimental objects. A magnetic gel was used as a tracer magnet, mixed as sodium alginate-Fe3O4 magnetic fluid and calcium gluconate solution. In short-term localization, a coaxial double-cavity puncture needle was applied to inject the gel into the lung after thoracotomy, and a pursuit magnet made of Nd-Fe-B permanent magnetic materials was used to attract the gel representing location of the nodule. In long-term localization, the gel was injected under X-ray guidance. Imaging changes to the lung were observed under X-ray daily. Thoracotomy was performed to excise tissue containing the gel, and hematoxylin-eosin staining was used to observe the tissue on postoperative days 1, 3, 5, and 7. Observe tissues morphology of heart, liver, spleen, and kidney in the same way. The gel was formed after injection and drew lung tissue to form a protrusion from the lung surface under the applied magnetic field. No complication was observed. The shape and position of the gel had not changed when viewed under X-ray. Pathological analysis showed the gel had a clear boundary without diffusion of magnetic fluid. All tissues retained good histologic morphology and no magnetic fluid was observed. Our study preliminarily suggested that the technique using sodium alginate-Fe3O4 magnetic gel to locate small pulmonary nodules with guidance of X-ray, and to search for them under an applied magnetic field during the operation is safe and feasible.


Assuntos
Neoplasias Pulmonares , Nódulos Pulmonares Múltiplos , Nódulo Pulmonar Solitário , Alginatos , Animais , Neoplasias Pulmonares/patologia , Nódulos Pulmonares Múltiplos/patologia , Coelhos , Estudos Retrospectivos , Nódulo Pulmonar Solitário/patologia , Cirurgia Torácica Vídeoassistida , Tomografia Computadorizada por Raios X/métodos
10.
Tissue Cell ; 76: 101750, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35182988

RESUMO

Kinesin family member 26B (KIF26B) is reported differently expressed in multiple neoplasms and exerts a pivotal role in carcinogenesis. To date, the relationship between KIF26B and non-small cell lung cancer (NSCLC) is unaddressed. This study explored the possible roles and mechanisms of KIF26B in NSCLC. We observed high levels of KIF26B in NSCLC, and demonstrated that high KIF26B levels predicted an overall shorter duration of survival. Functional experiments demonstrated that restraint of KIF26B by gene knockdown exhibited remarkable tumor-suppressive effects in NSCLC in vitro, including repression of cell proliferation, induction of G0/G1 cell cycle arrest, suppression of cell invasion and epithelial-mesenchymal transition, and enhancement of chemotherapeutic sensitivity. The study further revealed that inhibition of KIF26B was able to affect the activation of ß-catenin via regulation of the AKT/GSK-3ß axis. Moreover, forced expression of ß-catenin could reverse KIF26B-silencing-evoked tumor-suppressive effects. Importantly, NSCLC cells with KIF26B silencing exhibited decreased growth potential in nude mice in vivo. Collectively, our data indicate that restraint of KIF26B has a tumor-suppressive role in NSCLC by affecting the AKT/GSK-3ß/ß-catenin pathway. This work unveils a pivotal role of KIF26B in NSCLC and suggests it as a viable target for anti-NSCLC therapy.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Animais , Carcinoma Pulmonar de Células não Pequenas/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Glicogênio Sintase Quinase 3 beta/genética , Glicogênio Sintase Quinase 3 beta/metabolismo , Neoplasias Pulmonares/genética , Camundongos , Camundongos Nus , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Via de Sinalização Wnt/genética , beta Catenina/genética , beta Catenina/metabolismo
11.
Surg Endosc ; 36(5): 3653-3662, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35080676

RESUMO

BACKGROUND: Dissecting lymph nodes along the left recurrent laryngeal nerve (LRLN) is the most challenging step in thoracoscopic-assisted esophagectomy. To retract the proximal esophagus in the existing lymphadenectomy methods, either a special trocar is required to insert and take out endoscopic instruments or thoracic punctures are needed to externally retract the esophageal loop. Therefore, advanced skills for esophageal traction are important to facilitate the LRLN lymphadenectomy and to reduce the incidence of trauma to the chest wall. Herein, we present the magnetic anchoring and traction technique, a novel method for LRLN lymphadenectomy during thoracoscopic esophagectomy. METHODS: The magnetic anchoring traction system was successfully used to retract the upper thoracic esophagus and to help expose the upper mediastinum in 10 cases of thoracoscopic-assisted esophagectomy. When the external magnet was moved outside of body, the internal magnet was coupled with a magnetic force to pull the proximal esophagus to the appropriate direction, which helped to expose the LRLN and adjacent lymph nodes. The lymph nodes adjacent to the LRLN could then be dissected completely without any damage to the nerve. RESULTS: In all surgeries, the LRLN and adjacent lymph nodes were well visualized, and the number of trocars used to pass endoscopic instruments for retraction of the proximal esophagus or the number of thoracic punctures for external traction of the esophagus during the surgery were reduced. CONCLUSIONS: In thoracoscopic-assisted esophagectomy, the magnetic anchoring and traction technique can improve the exposure of the LRLN, facilitate LRLN lymphadenectomy, and reduce chest wall trauma.


Assuntos
Neoplasias Esofágicas , Nervo Laríngeo Recorrente , Neoplasias Esofágicas/cirurgia , Esofagectomia/métodos , Humanos , Excisão de Linfonodo/métodos , Fenômenos Magnéticos , Mediastino/patologia , Nervo Laríngeo Recorrente/patologia , Estudos Retrospectivos , Tração
12.
BMC Gastroenterol ; 21(1): 452, 2021 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-34861854

RESUMO

BACKGROUND: The incidence of congenital bronchoesophageal fistulas in adults is rare. Most fistulas discovered in adulthood are often small and can be repaired with a simple one-step method. CASE PRESENTATION: A 46-year-old female patient complained of a 2-month history of chocking, coughing, and a 12 kg drop in weight. The bronchofiberscopy and gastroscopy showed a large fistula, which extended from the esophagus to the main bronchus on both sides, thus forming a special three-way channel which has never been reported. This case was challenging both to the anesthetists and surgeons. The patient was intubated with a sengstaken-blakemore tube, and then received segmental esophageal resection, anastomotic reconstruction, and double-flap repair with esophagus segment in situ. CONCLUSION: When the fistula in BEF is large or complicated, appropriate surgical methods should be meticulously designed according to the condition of the patient. The problem of anesthesia intubation should be solved first, to allow a smooth operation. Secondly, a double-layer repair of the airway fistula by using esophageal wall tissues as patch materials is proposed.


Assuntos
Fístula Brônquica , Fístula Esofágica , Adulto , Anastomose Cirúrgica , Fístula Brônquica/etiologia , Fístula Brônquica/cirurgia , Tosse , Fístula Esofágica/etiologia , Fístula Esofágica/cirurgia , Feminino , Humanos , Pessoa de Meia-Idade
14.
Zhongguo Fei Ai Za Zhi ; 24(9): 613-622, 2021 Sep 20.
Artigo em Chinês | MEDLINE | ID: mdl-34256899

RESUMO

BACKGROUND: Lung cancer has the highest mortality in China. Different treatments are of great significance to the prognosis of patients. By comparing stage Ia non-small cell lung cancer (NSCLC) patients' survival rates for ablation and for sub-lobectomy, we studied the difference in the effects of the two treatments on patient prognosis. METHODS: Using the Surveillance, Epidemiology, and End Results (SEER) database, we screened eligible patients with stage Ia NSCLC from January 2004 to December 2015. Then, 228 patients treated with ablation and 228 patients treated with sub-lobotomy were then selected based on propensity score matching. After stratification, matching, and adjustment the Kaplan-Meier analysis was performed to compare the overall survival rates of patients treated with the two procedures. RESULTS: The Kaplan-Meier survival analysis showed that there is a significant difference between the ablation group and the sub-lobectomy group (P<0.05). In the univarlable analysis, the hazard ratio (HR) of sub-lobotomy group was 0.571 (95%CI: 0.455-0.717) compared with the ablation group. Patients treated with sub-lobectomy had a 0.571 times greater risk of adverse outcomes than those treated with ablation. In the multivariable analysis, the HR for sub-lobectomy group was 0.605 (95%CI: 0.477-0.766) compared with the ablation group. Patients treated with sub-lobectomy had a 0.605 time greater risk of adverse outcomes than those treated with ablation. The results suggested that the overall survival rate of patients with stage Ia NSCLC treated with sub-lobotomy was higher than that of patients treated with ablation. CONCLUSIONS: This study suggests that there is a significant difference in overall survival of stage Ia NSCLC patients treated with ablation and with sub-lobotomy. Patients treated with sub-lobotomy for stage Ia NSCLC had higher overall survival than those treated with ablation.


Assuntos
Técnicas de Ablação , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Pneumonectomia , Técnicas de Ablação/estatística & dados numéricos , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/epidemiologia , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Feminino , Humanos , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Pneumonectomia/estatística & dados numéricos , Prognóstico , Programa de SEER/estatística & dados numéricos , Estados Unidos/epidemiologia
15.
Lancet Respir Med ; 9(9): 1021-1029, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34280355

RESUMO

BACKGROUND: Icotinib has provided survival benefits for patients with advanced, epidermal growth factor receptor (EGFR)-mutant non-small-cell lung cancer (NSCLC). We aimed to compare icotinib with chemotherapy in patients with EGFR-mutant stage II-IIIA NSCLC after complete tumour resection. Here, we report the results from the preplanned interim analysis of the study. METHODS: In this multicentre, randomised, open-label, phase 3 trial done at 29 hospitals in China, eligible patients were aged 18-70 years, had histopathogically confirmed stage II-IIIA NSCLC, had complete resection up to 8 weeks before random assignment, were treatment-naive, and had confirmed activation mutation in exon 19 or exon 21 of the EGFR gene. Participants were randomly assigned (1:1) with an interactive web-based response system to receive either oral icotinib 125 mg thrice daily for 2 years or four 21-day cycles of intravenous chemotherapy (vinorelbine 25 mg/m2 on days 1 and 8 of each cycle plus cisplatin 75 mg/m2 on day 1 of each cycle for adenocarcinoma or squamous carcinoma; or pemetrexed 500 mg/m2 plus cisplatin 75 mg/m2 on day 1 every 3 weeks for non-squamous carcinoma). The primary endpoint was disease-free survival assessed in the full analysis set. Secondary endpoints were overall survival assessed in the full analysis set and safety assessed in all participants who received study drug. This trial is registered with ClinicalTrials.gov, NCT02448797. FINDINGS: Between June 8, 2015, and August 2, 2019, 322 patients were randomly assigned to icotinib (n=161) or chemotherapy (n=161); the full analysis set included 151 patients in the icotinib group and 132 in the chemotherapy group. Median follow-up in the full analysis set was 24·9 months (IQR 16·6-36·4). 40 (26%) of 151 patients in the icotinib group and 58 (44%) of 132 patients in the chemotherapy group had disease relapse or death. Median disease-free survival was 47·0 months (95% CI 36·4-not reached) in the icotinib group and 22·1 months (16·8-30·4) in the chemotherapy group (stratified hazard ratio [HR] 0·36 [95% CI 0·24-0·55]; p<0·0001). 3-year disease-free survival was 63·9% (95% CI 51·8-73·7) in the icotinib group and 32·5% (21·3-44·2) in the chemotherapy group. Overall survival data are immature with 14 (9%) deaths in the icotinib group and 14 (11%) deaths in the chemotherapy. The HR for overall survival was 0·91 (95% CI 0·42-1·94) in the full analysis set. Treatment-related serious adverse events occurred in two (1%) of 156 patients in the icotinib group and 19 (14%) of 139 patients in the chemotherapy group. No interstitial pneumonia or treatment-related death was observed in either group. INTERPRETATION: Our results suggest that compared with chemotherapy, icotinib significantly improves disease-free survival and has a better tolerability profile in patients with EGFR-mutant stage II-IIIA NSCLC after complete tumour resection. FUNDING: Betta Pharmaceuticals TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Quimioterapia Adjuvante/métodos , Éteres de Coroa/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Quinazolinas/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/mortalidade , China , Receptores ErbB/genética , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Mutação/genética , Resultado do Tratamento
16.
Am J Transl Res ; 13(3): 1411-1421, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33841666

RESUMO

Nampt consists of iNampt and eNampt, might contribute to modulating obesity-related malignancies and impairing response to chemotherapy in a range of cancers. This study explored the role of Nampt and adiposity in the progression and response to neo-adjuvant chemotherapy of esophageal squamous cell carcinoma (ESCC). Patients with ESCC were treated with 2 cycles of neo-adjuvant chemotherapy, then evaluated for surgery. Tumor regression grading (TRG) and prognosis of these patients were collected. Anthropometry was well utilized. Serum eNampt was determined by enzyme-linked immunosorbent assay, iNampt expression in tissues were assessed by PCR, western blot and immunohistochemistry. eNampt in sera elevated significantly in these over-weight or obese patients, and was positively associated with body mass index (BMI), waist circumference, visceral fat area (VFA), subcutaneous fat area (SFA) and total fat area (TFA) (P<0.05). iNampt expression in the mRNA and protein levels were up-regulated in ESCC compared to their adjacent non-tumor specimens (P<0.05). iNampt protein staining revealed mainly in the cytoplasm and nuclei, while it was not related to serum eNampt, BMI, waist circumference, VFA, SFA and TFA (P>0.05). Pre-treatment iNampt, BMI, SFA, TFA and age significantly correlated with neo-adjuvant chemotherapy response, and iNampt expression and age were independent predictors (P<0.05). Pre-treatment iNampt, ypT, ypN, ypTNM stage and TRG were associated with the survival of ESCCs, and ypN stage and TRG were independent prognostic factors (P<0.05). In conclusion, iNampt impaired ESCC response to neo-adjuvant chemotherapy independent of eNampt, targeting iNampt to increase ESCC response to neo-adjuvant chemotherapy would improve the prognosis of ESCCs.

17.
J Gastrointest Oncol ; 12(1): 11-27, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33708421

RESUMO

BACKGROUND: The Competing endogenous RNA (CeRNA) network plays important roles in the development and progression of multiple human cancers. Increasing attention has been paid to CeRNA in esophageal carcinoma (ESCA). METHODS: We explored The Cancer Genome Atlas (TCGA) database and then analyzed the RNAs of 142 samples to obtain long non-coding RNAs (lncRNAs), micro RNAs (miRNAs), and messenger RNAs (mRNAs) with different expression trends alongside the progress of ESCA. A series test of cluster (STC) analysis was carried out to identify a set of unique model expression tendencies. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were used to validate the function of key genes that were obtained from the STC analysis. RESULTS: Through our analysis, 272 lncRNAs, 87 miRNAs, and 692 mRNAs showed upward expression or downward expression trends, and these molecules were tightly involved in cell cycle, pathways in cancer, metabolic processes, and protein phosphorylation, among others. Ultimately, we constructed a CeRNA network containing a total of 71 lncRNAs, 56 miRNAs, and 125 mRNAs. The overall survival (OS) was analyzed using univariate Cox regression analysis to clarify the relationship between these key molecules from the CeRNA network and the prognosis of ESCA patients. Through survival analysis, we finally screened out two lncRNAs (DLEU2, RP11-890B15.3), three miRNAs (miR-26b-3p, miR-92a-3p, miR-324-5p), and one mRNA (SIK2) as crucial prognostic factors for ESCA. CONCLUSIONS: The novel CeRNA network that we constructed will provide new novel prognostic biomarkers and therapeutic targets for patients with ESCA.

18.
Zhongguo Yi Liao Qi Xie Za Zhi ; 45(1): 32-36, 2021 Feb 08.
Artigo em Chinês | MEDLINE | ID: mdl-33522173

RESUMO

The magnetic anchoring lung nodule positioning device is composed of a target magnet, an anchor magnet, a coaxial puncture needle and a puncture navigation template, through these, a new type of accurate positioning technology for small pulmonary nodules is derived. The device inserts the target magnet into the both sides nearby the lung nodule under the guidance of CT. Helped by the mutual attraction of the two target magnets, they can be fixed in the lung tissue, avoiding the movement in the lung, and accurately positioning the target lung nodule before surgery. In thoracoscopic surgery, the anchor magnet and the target magnet attract each other to achieve the purpose of positioning the target nodule. The device uses the characteristics of non-contact suction of magnetic materials biomedical engineering technology, eliminating the previous procedure of direct interaction with the positioning marks, finally achieves the target of precise positioning of lung nodules and rapid surgical removal.


Assuntos
Nódulo Pulmonar Solitário , Humanos , Pulmão , Neoplasias Pulmonares , Fenômenos Magnéticos , Imãs , Cirurgia Torácica Vídeoassistida , Tomografia Computadorizada por Raios X
19.
Cell Death Dis ; 12(1): 90, 2021 01 18.
Artigo em Inglês | MEDLINE | ID: mdl-33462197

RESUMO

Oxaliplatin resistance undermines its curative effects on cancer and usually leads to local recurrence. The oxidative stress induced DNA damage repair response is an important mechanism for inducing oxaliplatin resistance by activating autophagy. ELISA is used to detect target genes expression. TMT-based quantitative proteomic analysis was used to investigate the potential mechanisms involved in NORAD interactions based on GO analysis. Transwell assays and apoptosis flow cytometry were used for biological function analysis. CCK-8 was used to calculate IC50 and resistance index (RI) values. Dual-luciferase reporter gene assay, RIP and ChIP assays, and RNA pull-down were used to detect the interaction. Autophagy flux was evaluated using electron microscope and western blotting. Oxidative stress was enhanced by oxaliplatin; and oxaliplatin resistance gastric cancer cell showed lower oxidative stress. TMT labeling showed that NORAD may regulate autophagy flux. NORAD was highly expressed in oxaliplatin-resistant tissues. In vitro experiments indicate that NORAD knockdown decreases the RI (Resistance Index). Oxaliplatin induces oxidative stress and upregulates the expression of NORAD. SGC-7901 shows enhanced oxidative stress than oxaliplatin-resistant cells (SGC-7901-R). NORAD, activated by H3K27ac and CREBBP, enhanced the autophagy flux in SGC-7901-R to suppress the oxidative stress. NORAD binds to miR-433-3p and thereby stabilize the ATG5- ATG12 complex. Our findings illustrate that NORAD, activated by the oxidative stress, can positively regulate ATG5 and ATG12 and enhance the autophagy flux by sponging miR-433-3p. NORAD may be a potential biomarker for predicting oxaliplatin resistance and mediating oxidative stress, and provides therapeutic targets for reversing oxaliplatin resistance.


Assuntos
Histonas/metabolismo , MicroRNAs/metabolismo , Oxaliplatina/farmacologia , RNA Longo não Codificante/biossíntese , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/metabolismo , Animais , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Dano ao DNA , Reparo do DNA , Xenoenxertos , Histonas/genética , Humanos , Camundongos , Camundongos Nus , MicroRNAs/genética , Estresse Oxidativo/fisiologia , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Transdução de Sinais , Neoplasias Gástricas/genética , Regulação para Cima
20.
Transl Lung Cancer Res ; 10(11): 4057-4083, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35004239

RESUMO

Chest wall tumors are a relatively uncommon disease in clinical practice. Most of the published studies about chest wall tumors are usually single-center retrospective studies, involving few patients. Therefore, evidences regarding clinical conclusions about chest wall tumors are lacking, and some controversial issues have still to be agreed upon. In January 2019, 73 experts in thoracic surgery, plastic surgery, science, and engineering jointly released the Chinese Expert Consensus on Chest Wall Tumor Resection and Chest Wall Reconstruction (2018 edition). After that, numerous experts put forward new perspectives on some academic issues in this version of the consensus, pointing out the necessity to further discuss the points of contention. Thus, we conducted a survey through the administration of a questionnaire among 85 experts in the world. Consensus has been reached on some major points as follows. (I) Wide excision should be performed for desmoid tumor (DT) of chest wall. After excluding the distant metastasis by multi-disciplinary team, solitary sternal plasmacytoma can be treated with extensive resection and adjuvant radiotherapy. (II) Wide excision with above 2 cm margin distance should be attempted to obtain R0 resection margin for chest wall tumor unless the tumor involves vital organs or structures, including the great vessels, heart, trachea, joints, and spine. (III) For patients with chest wall tumors undergoing unplanned excision (UE) for the first time, it is necessary to carry out wide excision as soon as possible within 1-3 months following the previous surgery. (IV) Current Tumor Node Metastasis staging criteria (American Joint Committee on Cancer) of bone tumor and soft tissue sarcoma are not suitable for chest wall sarcomas. (V) It is necessary to use rigid implants for chest wall reconstruction once the maximum diameter of the chest wall defect exceeds 5 cm in adults and adolescents. (VI) For non-small cell lung cancer (NSCLC) invading the chest wall, wide excision with neoadjuvant and/or adjuvant therapy are recommended for patients with stage T3-4N0-1M0. As clear guidelines are lacking, these consensus statements on controversial issues on chest wall tumors and resection could possibly serve as further guidance in clinical practice during the upcoming years.

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