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BACKGROUND: The McKeown minimally invasive esophagectomy (McMIE) procedure has various limitations, including surgical contraindications and a high rate of postoperative pulmonary complications. A novel mediastinoscopic esophagectomy procedure was described in this study by using esophageal invagination and a transhiatal and bilateral cervical approach (EITHBC). METHODS: According to the mode of operation, a total of 259 patients were divided into two groups, among which 106 underwent EITHBC and 153 underwent McMIE. The number of lymph nodes dissected, intraoperative outcomes, and postoperative outcomes were compared between the two groups of patients. RESULTS: The results revealed that the average number of resected lymph node in the EITHBC group was significantly higher in the recL106 and TbL106 stations (recL106: 1.75 vs. 1.51, p = 0.016, TbL106: 1.53 vs. 1.19, p = 0.016) and significantly lower in the 107 stations (1. 74 vs. 2. 07, p < 0.001) than in the McMIE group. The intraoperative blood loss in the EITHBC group was significantly lower than that in the McMIE group (63.30 vs. 80.45 mL, p < 0.001). The incidence of postoperative pulmonary complications in the EITHBC group was lower than that in the McMIE group (14.15% vs. 27.45%, p = 0.008). The incidence of recurrent laryngeal nerve paralysis in the EITHBC group was significantly higher than that in the McMIE group (26.41% vs. 10.46%, p = 0.003). CONCLUSION: Compared with the McMIE procedure, the EITHBC procedure has advantages in terms of removing the upper mediastinal lymph nodes and reducing postoperative pulmonary complications.
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Neoplasias Esofágicas , Esofagectomia , Mediastinoscopia , Humanos , Esofagectomia/métodos , Feminino , Estudos Retrospectivos , Masculino , Mediastinoscopia/métodos , Pessoa de Meia-Idade , Neoplasias Esofágicas/cirurgia , Neoplasias Esofágicas/patologia , Idoso , Complicações Pós-Operatórias/epidemiologia , Excisão de Linfonodo/métodos , Resultado do Tratamento , Adulto , Estudos de CoortesRESUMO
PIK3CB is abnormally expressed in various carcinomas and affects the proliferation, invasion and drug resistance of cancer cells. However, its role in oesophageal squamous cell carcinoma (ESCC) is still unclear. In this study, PIK3CB was found to be highly expressed in ESCC tissues and cells and positively correlated with the poor prognosis of ESCC. Silencing PIK3CB inhibited the proliferation of ESCC cells, arrested the cell cycle, and promoted apoptosis. Mechanistic studies showed that the tumour-promoting effect of PIK3CB was achieved through PI3K/AKT/mTOR signalling pathway activation. Moreover, the high PIK3CB expression level in ESCC may be closely associated with the hypomethylation status of the gene promoter. In conclusion, PIK3CB promotes ESCC by activating the PI3K/AKT/mTOR signalling axis. PIK3CB may be a potential target in ESCC.
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Carcinoma de Células Escamosas , Neoplasias Esofágicas , Carcinoma de Células Escamosas/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/genética , Classe I de Fosfatidilinositol 3-Quinases/genética , Classe I de Fosfatidilinositol 3-Quinases/metabolismo , Neoplasias Esofágicas/patologia , Regulação Neoplásica da Expressão Gênica , Humanos , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Serina-Treonina Quinases TOR/metabolismoRESUMO
The deregulation of circular RNAs (circRNAs) is involved in cancer development. CircRNA polo-like kinase 1 (circPLK1) was reported to promote breast cancer development. However, the role of circPLK1 in malignant pleural mesothelioma (MPM) is unclear. The expression of circPLK1, miR-1294, and high mobility group AT-hook 1 (HMGA1) mRNA was measured by quantitative real-time PCR (qPCR). Cell viability was detected by CCK-8 assay. Colony formation ability was monitored by colony formation assay. Cell proliferation was detected by EdU assay. Cell migration and cell invasion were monitored by transwell assay. Cancer cell stemness was investigated by sphere formation assay. The protein levels of marker proteins and HMGA1 expression were measured by western blot analysis. The binding relationship between miR-1294 and circPLK1 or HMGA1 was validated by pull-down assay, dual-luciferase reporter assay or RIP assy. Animal study was performed to disclose the role of circPLK1 in vivo. Exosomes were identified by transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA). CircPLK1 was upregulated in MPM tumor tissues and cell lines. CircPLK1 knockdown suppressed the proliferation, migration, invasion and stemness of MPM cells. CircPLK1 contained a binding site for miR-1294 and thus bound to miR-1294 to sequester its expression. Inhibition of miR-1294 reversed the effects of circPLK1 knockdown. HMGA1 was a target of miR-1294, and circPLK1 bound to miR-1294 to increase the expression of HMGA1. MiR-1294 restoration also suppressed the proliferation, migration, invasion and stemness of MPM cells, while these effects were abolished by HMGA1 overexpression. In addition, circPLK1 knockdown inhibited tumor growth in vivo. CircPLK1 was overexpressed in exosomes derived from serum of MPM patients. CircPLK1 knockdown inhibited MPM cell proliferation, migration, invasion and stemness by targeting the miR-1294/HMGA1 pathway.
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Mesotelioma Maligno , MicroRNAs , Animais , Carcinogênese/genética , Carcinógenos , Regulação Neoplásica da Expressão Gênica , Proteína HMGA1a/genética , Proteína HMGA1a/metabolismo , MicroRNAs/metabolismo , RNA Circular , Fatores de Transcrição/genéticaRESUMO
OBJECTIVE: To compare the difference of health-related quality of life after oncologic esophagectomy between the patients using Jiang's gastroesophageal anastomosis and traditional end-to-end gastroesophageal anastomosis. METHODS: A total of 419 patients (223 in Jiang's anastomosis group, and 196 in end-to-end anastomosis group) underwent minimal invasive esophagectomy with cervical anastomosis from October 2012 to August 2016. All patients received radical esophageal cancer resection and cervical anastomosis. EORTC-QLQ-C30 and QLQ-OES18 were used to assess the health-related quality of life at the 1st, 3rd, 6th, 12th, 24th month after esophagectomy. RESULTS: There were 25 dimensions and items in EORTC-QLQ-C30 and QLQ-OES18. The postoperative quality of life decreased obviously at the 1st month and then recovered obviously at the 6th month after the surgery, and it ranged small at the 12th and 24th month. Compared with end-to-end anastomosis group, Jiang's anastomosis group had less reflux and less cough at the 1st month (P=0.023, P=0.010) and the 3rd month (P=0.004, P=0.013), then had better emotional function, less reflux and less cough at the 6th month (P=0.013, P=0.014, P=0.043), better emotional function, less nausea, and less reflux at the 12th month(P=0.004, P=0.023, P=0.021), as well as less reflux at the 24th month (P=0.020). There was no significant difference in other dimensions and items between the two groups during the follow-up period. CONCLUSION: Jiang's anastomosis is safe and feasible, and could improve the postoperative quality of life of the patients with esophagectomy. It is worth to further application in clinical practice.
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Neoplasias Esofágicas , Refluxo Gastroesofágico , Anastomose Cirúrgica , Esofagectomia , Humanos , Qualidade de VidaRESUMO
BACKGROUND: Neoadjuvant immunotherapy has ushered in a new era of perioperative treatment for resectable non-small cell lung cancer (NSCLC). However, large-scale data for verifying the efficacy and optimizing the therapeutic strategies of neoadjuvant immunochemotherapy in routine clinical practice are scarce. METHODS: NeoR-World (NCT05974007) was a multicenter, retrospective cohort study involving patients who received neoadjuvant immunotherapy plus chemotherapy or chemotherapy alone in routine clinical practice from 11 medical centers in China between January 2010 and March 2022. Propensity score matching was performed to address indication bias. RESULTS: A total of 408 patients receiving neoadjuvant immunochemotherapy and 684 patients receiving neoadjuvant chemotherapy were included. The pathologic complete response (pCR) and major pathologic response (MPR) rates of the real-world neoadjuvant immunochemotherapy cohort were 32.8% and 58.1%, respectively. Notably, patients with squamous cell carcinoma exhibited significantly higher pCR and MPR rates than those with adenocarcinoma (pCR, 39.2% vs 16.5% [P < .001]; MPR, 66.6% vs 36.5% [P < .001]), whereas pCR and MPR rates were comparable among patients receiving different neoadjuvant cycles. In addition, the 2-year rates of disease-free survival (DFS) and overall survival (OS) rate were 82.0% and 93.1%, respectively. Multivariate analyses identified adjuvant therapy as an independent prognostic factor for DFS (hazard ratio [HR], 0.51; 95% confidence interval [CI], 0.29-0.89; P = .018) and OS (HR, 0.28; 95% CI, 0.13-0.58; P < .001). A significantly longer DFS with adjuvant therapy was observed in patients with non-pCR or 2 neoadjuvant cycles. We observed significant benefits in pCR rate (32.4% vs 6.4%; P < .001), DFS (HR, 0.50; 95% CI, 0.38-0.68; P < .001) and OS (HR, 0.61; 95% CI, 0.40-0.94; P = .024) with immunotherapy plus chemotherapy compared to chemotherapy alone both in the primary propensity-matched cohort and across most key subgroups. CONCLUSIONS: The study validates the superior efficacy of neoadjuvant immunochemotherapy over chemotherapy alone for NSCLC. Adjuvant therapy could prolong DFS in patients receiving neoadjuvant immunochemotherapy, and patients with non-pCR or those who underwent 2 neoadjuvant cycles were identified as potential beneficiaries of adjuvant therapy.
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Lung cancer is one of the most commonly diagnosed cancers, and surgical resection is the optimal choice for the primary lung tumor. But for the secondary lung cancer, chemotherapy and combined radiotherapy still are the main strategies. To realize the combined treatment for non-small cell lung cancer (NSCLC), in this work, a nanoplatform based on pemetrexed (PE)-loaded mesoporous polydopamine (MPDA) nanoparticles were investigated. PE, a special therapeutic drug for NSCLC, was loaded into the MPDA nanoparticles via electrostatic attraction and was encapsulated with polyvinyl pyrrolidone (PVP). The results showed that, when irradiating with 808 nm near-infrared light, the PE loaded MPDA (MPDA@PE@PVP) nanoparticles have excellent photothermal conversion properties, which would result in increase of ambient temperature and could accelerate the release of PE. In vitro cell experiments proved that MPDA@PE@PVP nanoparticles have excellent killing ability for NSCLC A549 cells by the functions of PE and photothermal ability of MPDA nanoparticles. Meanwhile, the intra-cellular reactive oxygen species (ROS) levels of A549 cells in the MPDA@PE@PVP nanoparticle-treated group could be promoted significantly after irradiation, leading to the death of A549 cells. In vivo animal model results showed that MPDA@PE@PVP nanoparticles could gather at the tumor site by enhanced permeability and retention (EPR) effect and have significant inhibition ability for lung tumor by synergistic therapy of chemotherapy, photothermal therapy and photodynamic therapy.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Pemetrexede/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológicoRESUMO
Esophageal squamous cell carcinoma (ESCC), which accounts for 90% of esophageal carcinomas, seriously endangers human health. Worse still, the 5-year overall survival of ESCC is approximately 20%. Elucidation of the potential mechanism and exploration of promising drugs for ESCC are urgently needed. In this study, a high level of exosomal PIK3CB protein was found in the plasma of ESCC patients, which might indicate a poor prognosis. Moreover, a significant Pearson's correlation was observed at the protein level between exosomal PIK3CB and exosomal PD-L1. Further study revealed that cancer cell-intrinsic and exosome-derived PIK3CB promoted the transcriptional activity of the PD-L1 promoter in ESCC cells. Moreover, treatment with exosomes with lower levels of exosomal PIK3CB decreased the protein level of the mesenchymal marker ß-catenin while increasing that of the epithelial marker claudin-1, indicating the potential regulation of epithelial-mesenchymal transition. Consequently, the migratory ability and cancer stemness of ESCC cells and the growth of tumors formed by ESCC cells were decreased with the downregulation of exosomal PIK3CB. Therefore, exosomal PIK3CB plays an oncogenic role by promoting PD-L1 expression and malignant transformation in ESCC. This study may provide new insight into the inherent biological aggressiveness and the poor response to currently available therapies of ESCC. Exosomal PIK3CB may be a promising target for the diagnosis and therapy of ESCC in the future.
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Carcinoma de Células Escamosas , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Humanos , Carcinoma de Células Escamosas do Esôfago/genética , Carcinoma de Células Escamosas do Esôfago/patologia , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas/patologia , Antígeno B7-H1/genética , Antígeno B7-H1/metabolismo , Prognóstico , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Proliferação de Células , Classe I de Fosfatidilinositol 3-Quinases/genética , Classe I de Fosfatidilinositol 3-Quinases/metabolismoRESUMO
INTRODUCTION: Lung cancer is one of the most common cancer malignancies and the principal cause of cancer-associated deaths worldwide. Non-small cell lung cancers (NSCLCs) account for more than 80% of all lung cancer cases. Recent studies showed that the genes of the integrin alpha (α) (ITGA) subfamily play a fundamental role in various cancers. However, little is known about the expression and roles of distinct ITGA proteins in NSCLCs. METHODS: Gene Expression Profiling Interactive Analysis and UALCAN (University of ALabama at Birmingham CANcer) web resources and The Cancer Genome Atlas (TCGA), ONCOMINE, cBioPortal, GeneMANIA, and Tumor Immune Estimation Resource databases were used to evaluate differential expression, correlations between the expression levels of individual genes, the prognostic value of overall survival (OS) and stage, genetic alterations, protein-protein interactions, and the immune cell infiltration of ITGAs in NSCLCs. We used R (v. 4.0.3) software to conduct gene correlation, gene enrichment, and clinical correlation of RNA sequencing data of 1016 NSCLCs from TCGA. To evaluate the expression of ITGA5/8/9/L at the expression and protein levels, qRT-PCR, immunohistochemistry (IHC), and hematoxylin and eosin (H&E) were performed, respectively. RESULTS: Upregulated levels of ITGA11 messenger RNA and downregulated levels of ITGA1/3/5/7/8/9/L/M/X were observed in the NSCLC tissues. Lower expression of ITGA5/6/8/9/10/D/L was discovered to be expressively associated with advanced tumor stage or poor patient prognosis in patients with NSCLC. A high mutation rate (44%) of the ITGA family was observed in the NSCLCs. Gene Ontology functional enrichment analyses results revealed that the differentially expressed ITGAs could be involved in roles related to extracellular matrix (ECM) organization, collagen-containing ECM cellular components, and ECM structural constituent molecular functions. The results of the Kyoto Encyclopedia of Genes and Genomes analysis revealed that ITGAs may be involved in focal adhesion, ECM-receptor interaction, and amoebiasis; the expression of ITGAs was significantly correlated with the infiltration of diverse immune cells in NSCLCs. ITGA5/8/9/L was also highly correlated with PD-L1 expression. The validation results for marker gene expression in NSCLC tissues by qRT-PCR, IHC, and H&E staining indicated that the expression of ITGA5/8/9/L decreased compared with that in normal tissues. CONCLUSION: As potential prognostic biomarkers in NSCLCs, ITGA5/8/9/L may fulfill important roles in regulating tumor progression and immune cell infiltration.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/genética , PrognósticoRESUMO
Objective: To understand the characteristics of genetic mutation in multiple primary lung cancer so as to guide clinical decisions in targeted therapy. Methods: We analyzed a total of 265 tumors from 111 patients who underwent surgery for multiple lung cancers. Individual tumors were subjected to histological evaluation and gene mutation analysis using ABI 7500 Fluorescence quantitative PCR. Results: In this study, we analyzed demographic and clinical parameters such as age, gender, smoking, alcohol consumption, pathological type, number of nodules, and other details of 111 patients with early multiple primary lung cancer. We also compared the clinicopathologic characteristics of different populations based on the gene mutation status of pulmonary nodules. Subsequently, we performed a clinicopathological analysis of all 265 pulmonary nodules from these patients. Results showed significant differences in clinicopathological features of pulmonary nodules in different genetic mutations. Conclusion: This study revealed the gene mutation characteristics and clinicopathological features in early multiple primary lung cancer. We found that the gene mutation status between different nodules in patients with early multiple primary lung cancer was inconsistent in most cases. Therefore, the use of targeted therapy based on the genetic sequencing of only one nodule, is unreliable. We hope this study can be helpful in guiding clinical treatment decisions.
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Background: Camrelizumab plus chemotherapy have been approved as standards for the treatment of advanced non-small cell lung cancer (NSCLC) patients based on two phase III trials. However, clinical trial results may not be representative of the general population, as clinical trials often have specific inclusion and exclusion criteria. Our research aims to investigate the real-world effectiveness and safety of camrelizumab in inoperable or advanced NSCLC patients. Methods: This multicenter retrospective observational study included inoperable or advanced pathologically confirmed NSCLC patients who received at least one dose of camrelizumab at 22 hospitals. Clinical and follow-up data of camrelizumab were collected retrospectively from the medical records. The primary outcome was the objective response rate (ORR) and secondary outcomes were disease control rate (DCR), 6-month progression-free survival (PFS), overall survival (OS), and treatment-related adverse events (TRAEs). Multivariate logistic and Cox regression analyses were applied to identify potential predictive factors of ORR and PFS, respectively. Results: Between July 2019 and March 2021, 336 patients were included. Adenocarcinoma was seen in 58.4% and stage IV disease in 69.3%. Twenty-nine (8.6%) had liver metastasis at baseline. Most patients received camrelizumab in the first-line setting (74.1%) and in combination with chemotherapy (60.7%). The ORR was 40.2% [95% confidence interval (CI): 34.9-45.6%] and DCR was 85.1% (95% CI: 81.3-88.9%), while the 6-month PFS and OS rates were 73.0% (95% CI: 67.1-78.0%) and 93.1% (95% CI: 89.8-95.4%), respectively. In multivariate analyses, liver metastasis [odds ratio (OR), 0.324; 95% CI: 0.115-0.915; P=0.033] and increasing lines of camrelizumab treatment (vs. first line, second line: OR, 0.347; 95% CI: 0.162-0.741; P=0.006; ≥ third line: OR, 0.126; 95% CI: 0.043-0.367; P<0.001) were negatively associated, while a longer duration of camrelizumab treatment was positively associated with ORR and PFS. TRAEs were recorded in 164 (48.8%) patients, without new safety signal. Conclusions: We conducted a comprehensive overview of the effectiveness and safety profile of camrelizumab in a broader NSCLC population in real world NSCLC patients, and subgroup analysis indicated the presence of liver metastasis was associated with worse outcomes.
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A middle-aged male received CT-guided lung nodule localization and segmentectomy for a 10-mm lesion in the right upper lung. He developed left side paralysis after surgery, which was proved to be cerebral artery air embolism caused by a CT-guided lung puncture. He achieved almost full recovery with hyperbaric oxygen therapy and intensive rehabilitation. This case highlights the possibility of cerebral artery air embolism during CT-guided lung nodule resection in hybrid theater, with emphasis on prevention and early detection of this life-threatening complication.
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Objective: The objective of this article is to assess the rate of anastomotic leak and other perioperative outcomes in patients undergoing esophagectomy with either thoracic or cervical anastomosis. Methods: This meta-analysis was conducted by searching relevant literature studies in Web of Science, Cochrane Library, PubMed, and Embase databases. Articles that included patients undergoing esophagectomy and compared perioperative outcomes of McKeown with Ivor Lewis procedures were included. The primary outcome parameter was anastomotic leak, and secondary outcome parameters were grade ≥2 anastomotic leak, chylothorax, recurrent laryngeal nerve injury, hospital length of stay, intensive care unit (ICU) length of stay, postoperative mortality rate, operative time, blood loss, R0 resection rate, and lymph nodes examined. Results: A total of eight studies, with 3,291 patients (1,857 Ivor Lewis procedure and 1,434 McKeown procedure) were eligible for analysis. Meta-analysis showed that Ivor Lewis procedure was associated with lower rate of anastomosis leak of all grades [risk ratio (RR), 0.67; 95% confidence interval (CI), 0.55-0.82; P = 0.0001], lower rate of recurrent laryngeal nerve injury (RR, 0.14; 95% CI, 0.08-0.25), and shorter length of hospital stay (weighted mean difference, 0.13; 95% CI, 0.04-0.22). Grade ≥2 anastomotic leak, chylothorax, ICU length of stay, postoperative mortality rate, operative time, blood loss, R0 resection rate, and lymph nodes examined were similar between the two groups. Conclusions: Although all grades of anastomotic leak and recurrent laryngeal nerve injury are higher in the McKeown procedure, this meta-analysis supports similar short-term outcomes and oncological efficacy between Ivor Lewis and McKeown esophagectomy.
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Esophageal squamous cell carcinoma (ESCC) remains a common aggressive malignancy in the world. Multiple studies have shown evidence to support the hypothesis that certain functional genes that are engaged in the microenvironment of tumors played a role in the progression of ESCC. Thus, to better analyze the prognostic values of important genes in ESCC, there is an immediate need for an in-depth research study. From the TCGA database, the RNA-seq data and clinical features of 163 ESCC patients were obtained. Using the ESTIMATE technique, we were able to calculate the ImmuneScore, the StromalScore, and the ESTIMATEScore for each ESCC sample. The samples from the ESCC were split up into high score and low score groups based on the median of the various scores. In this study, ImmuneScore, StromalScore, and ESTIMATEScore were not found to be linked with overall survival of ESCC patients, according to our findings. Higher StromalScores were linked to more advanced T stages and clinical stages. The intersection analysis that was exhibited by the use of a Venn diagram indicated that there was a total of 944 upregulated genes that shared the same high score in both the ImmuneScore and the StromalScore and that there was 0 downregulated gene that shared the same low score. Survival experiments confirmed MIR548P and TRAV39 as critical prognostic biomarkers for ESCC patients. Importantly, we found that TRAV39 expression was positively associated with T cell CD4 memory activated while negatively associated with B cell memory, dendritic cells activated, and mast cells activated. In addition, we found that MIR548P expression was negatively associated with mast cells activated while positively associated with T cell CD4 memory activated. Overall, we identified MIR548P and TRAV39 as new modulators for ESCC, affecting the immune microenvironment of ESCC patients and may be a target of immunotherapy.
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Objective: To explore the early oral food intake on the quality of life of postoperative patients with esophageal cancer. Methods: A total of 100 patients with esophageal cancer were randomized into an observation group and a control group, with 50 patients in each group. The patients in the control group were routinely indwelt with a gastric tube and fasted for seven days. If no abnormality was found in examinations, the patients were instructed to attempt drinking water and gradually try eating liquid, semi-liquid, and common foods. The patients in the observation group were subjected to the early oral food intake strategy. The recovery and gastrointestinal symptoms of the patients were evaluated using the six-minute walk test and gastrointestinal symptom rating scale (GSRS) at discharge. The quality of life of patients was evaluated using the QLQ-C30 scale and QLQ-OES18 scale during the return visit to the hospital one month after discharge. Results: The GSRS score of the observation group was markedly lower than that of the control group. The six-minute walk distance in the observation group was significantly higher than that in the control group; the difference was statistically significant (P < 0.01). In comparing the QLQ-C30 scores of the two groups, the scores in physical function, emotional function, and general health condition in the observation group were higher than those in the control group. In comparing the QLQ-OES18 scores of the two groups, the scores in dysphagia, eating, reflux, pain domains, and choking symptoms in the observation group were lower than those in the control group; the differences were statistically significant (P < 0.01), and there were no statistically significant differences in other symptoms and related functions between the two groups (P > 0.05). Conclusion: The early oral food intake strategy can reduce gastrointestinal symptoms, promote recovery of postoperative patients with esophageal cancer, and improve quality of life.
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Background: This study assessed the efficacy of transcervical and transhiatal esophagectomy versus thoracoscopic esophagectomy in patients with esophageal carcinoma (EC). Methods: A total of 80 patients with EC were enrolled in this study, including 40 cases in the observation group that received transcervical combine transhiatal esophagectomy and the rest 40 cases of the group that underwent thoracoscopic esophagectomy. The preoperative, intraoperative, and postoperative data were analyzed between the two surgeries, regarding perioperative bleeding, the total number of dissected mediastinal lymph nodes, operative time, number of lymph nodes in the left para-recurrent laryngeal nerve (para-RLN) or the right para-RLN, time in the intensive care unit (ICU), postoperative pain score, the length of postoperative stay (LOPS), PO2/fraction of inspired oxygen (PO2/FiO2), pulmonary infection, and lymphatic metastasis. Results: The operations were successfully performed in all 80 patients. The results showed that patients who underwent transcervical and transhiatal esophagectomy had shorter operations than those with transthoracic esophagectomy (200 minutes vs 235 minutes, Kruskal-Wallis test [Z] = -3.700, P < 0.001). The number of dissected mediastinal lymph nodes in the left para-RLN in the observation group was higher than in the control group (25.0% vs 2.5%, Z = 2.568, P = 0.010). The postoperative pain score day 1 (0.0% vs 17.5%, Z = -4.292, P < 0.001), postoperative pain score day 3 (12.5% vs 37.5%, Z = -3.363, P < 0.001) and 48-h PO2/FiO2 (290 minutes vs 255 minutes, Z = 3.747, P < 0.001) were significant between the two groups. The LOPS of patients with EC in the observation group was shorter than the control group (7 vs 8, Z = -2.119, P = 0.034). The number of patients receiving transcervical and transhiatal esophagectomy that developed postoperative pulmonary infections was less than the controls (chi-square [χ 2] = 4.114, P = 0.043). Moreover, the transcervical and transhiatal esophagectomy was an independent protect factor for postoperative pulmonary infection (odds ratio [OR] =7.801, P = 0.037). Conclusion: The transcervical and transhiatal esophagectomy is a good operation for treating patients with EC, which may offer an opportunity to treat cases who cannot have thoracotomy.
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OBJECTIVE: This study explores the value of the application of simultaneous localization of multiple pulmonary nodules in a hybrid operating room for uniportal video-assisted thoracic surgery (VATS). METHODS: This study performed a retrospective analysis of 60 patients with multiple pulmonary nodules (the number of nodules in every patient was ≥2, 131 in total) admitted to our hospital from September 2020 to September 2021. After computerized tomography (CT) scanning in a hybrid operating room, a multi-hook locating needle was used for simultaneous localization. The localization success, surgical resection, and locating needle unhooking rates of multiple pulmonary nodules were analyzed. The complication incidence, localization time, operation time, anesthesia time, post-isolation nodule search time, and postoperative hospital stay length were analyzed. In addition, the patients' anxieties about the puncture localization were evaluated. RESULTS: The intraoperative CT scans successfully showed all pulmonary nodules. The localization success, unhooking, and nodule resection rates were 98.5% (129/131), 1.5% (2/131), and 100% (131/131), respectively. The median times of the localization, operation, anesthesia, post-isolation pulmonary nodule search, and hospital stay were 19 min [interquartile range (IQR): 15-30 min], 98 min (IQR: 80-110 min), 149.5 min (IQR: 126-171 min), 3.5 min (IQR: 1-5 min), and 6 d (IQR: 4-9 d), respectively. The incidences of pneumothorax and pulmonary hemorrhage were 20.0% (12/60) and 13.3% (8/60), respectively. The self-rating anxiety scale score of the patients was 53.6 ± 6.1. CONCLUSION: The hybrid operating room could be beneficial in accurately localizing multiple pulmonary nodules with reasonable safety and patient tolerance, and it is applicable to uniportal VATS.
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Objective: This study aimed to design a nomogram survival prediction by means of the figures retrieved from the Surveillance, Epidemiology, and End Results (SEER) source bank, and to predict the overall survival (OS) of patients with stage IIA non-small cell lung cancer (NSCLC) after surgery. Methods: Data for 4511 patients who had been diagnosed with postoperative stage IIA NSCLC were collected from the SEER databank, while information on 528 patients was acquired from the Chongqing University Cancer Hospital for the external validation cohort. The independent risk factors that affected the prognosis were identified using a multivariate Cox proportional hazards regression model (also used to conduct a nomogram). A survival analysis between the low- and the high-risk groups was performed using the Kaplan-Meier method. Furthermore, a subgroup analysis was conducted of the two groups using the Kaplan-Meier method to determine whether the patients had received adjuvant chemotherapy. Results: The following five variables were integrated into the nomogram: sex (female: HR 1.73, 95% CI 0.64-0.83), age (≥60: HR 1.61, 95% CI 1.39-1.87), differentiation grade (grade II: HR 2.19, 95% CI 1.66-2.88; grade III: HR 2.65, 95% CI 2.00-3.51; grade IV: HR 3.17, 95% CI 1.99-5.03), surgery (lobectomy: HR 0.72, 95% CI 0.59-0.86), and lymph node resection (>12: HR 0.82, 95% CI 0.70-0.96). Furthermore, the patients selected were categorized into high- and low-risk groups. The OS rate was significantly lower in the high-risk group than in the low-risk group (P < 0.001). Finally, adjuvant chemotherapy was highly correlated with OS in the high-risk set (P = 0.035); however, adjuvant chemotherapy was not related to OS in the low-risk set. Conclusion: A nomogram was created as a reliable, convenient scheme that could predict OS, and it was determined that the high-risk feature patients identified by the nomogram gained benefits from adjuvant chemotherapy.
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Background: The prognostic value of the existing 8th edition post-neoadjuvant treatment (ypTNM) appears to be limited, and necessary reassessment and modification should be carried out as needed. This study aimed to compare the prognosis prediction accuracy of modified and unmodified versions of the 8th edition ypTNM. Methods: Esophageal cancer patients who had received neoadjuvant therapy from the Surveillance, Epidemiology, and End Results (SEER) database were included in this observational longitudinal study. The median follow-up time was 26 months. All-cause mortality was the outcome variable. Demographic and clinical variables were collected as covariates. Kaplan-Meier (log-rank test) and Cox proportional hazards models were conducted for developing modified ypTNM staging. The concordance index (C-index) was calculated to analyze the discriminative ability of modified ypTNM staging. Results: Overall, 3,595 patients met inclusion criteria. The 8th edition staging was not able to significantly discriminate between patients with ypT1- and ypT2-, ypT3- and ypT4-, ypN2- and ypN3- disease, respectively. Using the modified staging, we found that patients with ypT0-2 [hazard ratio (HR) =1.232; 95% confidence interval (CI): 1.053-1.441] and ypT3-4 (HR =1.257; 95% CI: 1.136-1.390) with grade III + IV had a significant risk of death compared to those with grade I + II. As was the case for the ypN0 (HR =1.295; 95% CI: 1.073-1.562) group with middle and upper tumor locations compared to those with low tumor location. The modified staging possessed better homogeneity in terms of the chi-square likelihood ratio (143.443 vs. 102.044), Akaike information criterion (AIC) (32,683.716 vs. 32,719.115), and Schwarz's Bayesian criterion (SBC) (32,723.496 vs. 32,741.847), as well as better discriminatory ability (C-index of 0.577 vs. 0.560, P=0.045) compared to the 8th edition staging. Conclusions: Although the modified ypTNM staging system we created by incorporating tumor grade and location to the original T and N displayed certain prognosis prediction accuracy compared with the 8th edition ypTNM staging, a larger sample size and prospective studies are needed to explore.
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OBJECTIVE: To observe the killing effect of recombinant type I herpes simplex virus (HSV-I) with Gibbon ape leukemia virus membrane fusion glycoprotein (GALV.fus) gene on lung adenocarcinoma in vitro and in vivo. METHODS: Recombinant HSV-I plasmids (HSV-UL38P-GALV.fus, HSV-CMVP-GALV.fus, HSV-CMVP-EGFP) was introduced into green monkey kidney cells (Vero) by liposome to amplify the virus, which were propagated in Vero cells and purified by cesium chloride density purification, titrated by TCID50 method. The three recombinant viruses were named as Synco-2, Synco-1 and Baco-1 respectively, and were transfected into lung adenocarcinoma cell line A549 cell and human lung adenocarcinoma xenografts which were established in nude mice subcutaneously to observe the expression and transfection of recombinant plasmids; mice model was divided to A (Control) group, B (Baco-1) group, C (Synco-1) group, D (Synco-2) group and E (Synco-2) group. The antitumor and cytotoxic effects of the virus in vitro or in vivo were investigated simultaneously. RESULTS: Recombinated HSV-I virus were packed successfully, the titre of Baco-1, Synco-1 and Synco-2 were 3 x 10(10) pfu/mL, 1X 10(11) pfu/mL and 4 x 10(10) pfu/mL respectively. The virus produced clear antitumor effects in vitro, the oncolytic activity of Synco-2 and Synco-1 was superior to that of Baco-1 (P < 0.01). The striking antitumor effect was seen when the virus was given subcutaneously in established xenografts in the animals. Tumor volume in Group C and D decreased significantly compared those in Group A and B (P < 0.01). The same result was observed in tumour weight (P < 0.01), and we also find that there was statistical significance between Group C and D in tumour quality at last two weeks (P < 0.01). CONCLUSIONS: The three recombinant HSV-I were packaged, amplificated and purified successfully. Recombinant GALV. fus gene system controlled by special promoter and mediated by available carrier has potent activity against lung cancer both in vitro or in vivo, and maybe a new promising candidate for investigative gene therapy of this malignancy.
Assuntos
Terapia Genética/métodos , Herpesvirus Humano 1/metabolismo , Vírus da Leucemia do Macaco Gibão/genética , Neoplasias Pulmonares/terapia , Glicoproteínas de Membrana/genética , Proteínas Virais de Fusão/farmacologia , Adenocarcinoma/patologia , Adenocarcinoma/terapia , Animais , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Chlorocebus aethiops , Herpesvirus Humano 1/genética , Humanos , Neoplasias Pulmonares/patologia , Glicoproteínas de Membrana/metabolismo , Camundongos , Camundongos Nus , Transplante de Neoplasias , Transfecção , Células Vero , Proteínas Virais de Fusão/genéticaRESUMO
OBJECTIVE: Esophageal cancer (ESCA) is one of the most aggressive malignancies globally with an undesirable five-year survival rate. Here, this study was conducted for determining specific functional genes linked with ESCA initiation and progression. METHODS: Gene expression profiling of ESCA was curated from TCGA (containing 160 ESCA and 11 nontumor specimens) and GSE38129 (30 paired ESCA and nontumor tissues) datasets. Differential expression analysis was conducted between ESCA and nontumor tissues with adjusted p value <0.05 and |log2fold-change|>1. Weighted gene coexpression network analysis (WGCNA) was conducted for determining the ESCA-specific coexpression modules and genes. Thereafter, ESCA-specific differentially expressed genes (DEGs) were intersected. Functional enrichment analysis was then presented with clusterProfiler package. Protein-protein interaction was conducted, and hub genes were determined. Association of hub genes with pathological staging was evaluated, and survival analysis was presented among ESCA patients. RESULTS: This study determined 91 ESCA-specific DEGs following intersection of DEGs and ESCA-specific genes in TCGA and GSE38129 datasets. They were remarkably linked to cell cycle progression and carcinogenic pathways like the p53 signaling pathway, cellular senescence, and apoptosis. Ten ESCA-specific hub genes were determined, containing ASPM, BUB1B, CCNA2, CDC20, CDK1, DLGAP5, KIF11, KIF20 A, TOP2A, and TPX2. They were prominently associated with pathological staging. Among them, KIF11 upregulation was in relation to undesirable prognosis of ESCA patients. CONCLUSION: Collectively, we determined ESCA-specific coexpression modules and hub genes, which offered the foundation for future research concerning the mechanistic basis of ESCA.