Transhiatal bilateral cervical approach for mediastinoscopy-assisted esophagectomy: A retrospective cohort study.

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.

Correlation between gene mutation status and clinicopathologic features in early multiple primary lung cancer.

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.

Systematic Analysis of the Prognostic Significance and Roles of the Integrin Alpha Family in Non-Small Cell Lung Cancers.

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.

A Population-Based Study on the Prognostic factors and Efficacy of Adjuvant Chemotherapy in the Postoperative Stage for Patients with Stage IIA Non-Small Cell Lung Cancer.

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.

Perioperative Clinical Results of Transcervical and Transhiatal Esophagectomy versus Thoracoscopic Esophagectomy in Patients with Esophageal Carcinoma: A Prospective, Randomized, Controlled Study.

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.

[Study on Health-related Quality of Life in Patients with Jiang's Gastroesophageal Anastomosis after Oncologic Esophagectomy].

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.

A novel technique for cervical gastro-oesophageal anastomosis during minimally invasive oesophagectomy.

BACKGROUND: Anastomotic leakage, fibrous stricture and gastro-oesophageal reflux are three major complications of gastro-oesophageal anastomosis, particularly in cervical anastomosis. Our aim was to evaluate the safety and efficacy of a novel cervical anastomosis technique (NA) by comparing it to traditional side-to-side anastomosis (SS) and end-to-side anastomosis using a circular stapler (CS) in terms of postoperative leakage, stricture and reflux. METHODS: A total of 390 patients with thoracic oesophageal cancer underwent minimally invasive oesophagectomy with cervical anastomosis (192 with NA, 34 with SS and 164 with CS) in our institute from January 2013 and May 2016. A detailed description of the surgical procedure is provided, and the major postoperative complications, including postoperative leakage, stricture and reflux, were compared using a three-armed controlled study. RESULTS: The anastomotic method was an independent risk factor for anastomotic leakage, as well as stricture and reflux. The rate of anastomotic leakage of the NA group (1.0%) was significantly lower than that in the SS group (8.8%, P = 0.025) and in the CS group (8.5%, P = 0.001). The rate of anastomotic stricture in the NA group was not significantly different than that in the SS group (1.5% vs. 2.9%, P = 0.368) but was significantly lower than that in the CS group (1.5% vs. 18.9%, P < 0.001). The incidence of gastro-oesophageal reflux in the NA group was significantly lower than that in the SS group and the CS group (5.7% vs. 23.5% and 18.3%, P = 0.003 and 0.001, respectively). CONCLUSION: Jiang's anastomosis technique remarkably reduces the incidence of gastro-oesophageal anastomotic leakage, stricture and reflux, and it is a safe and effective technique for minimally invasive oesophagectomy.

Killing effect of TNF-mediated by conditionally replicating adenovirus on esophageal cancer and lung cancer cell lines.

OBJECTIVE: The killing effect of TNF mediated by conditionally replicating adenovirus SG502 on human cancer cell lines was assessed by in vivo and in vitro experiments. METHODS: The recombinant adenovirus SG502-TNF was used to infect human lung cancer cell line A549 and human esophageal cancer cell line TE-1. The expression of the exogenous gene and its inhibitory effect on the tumor cell lines were thus detected. Tumor transplantation experiment was performed in mice with the purpose of assessing the inhibitory effect of the adenovirus on tumor cells and tumor formation. The targeting of the adenovirus and the mechanism of tumor inhibition were discussed by in vivo imaging technology, HE staining and TUNEL assay. RESULTS: Recombinant adenovirus SG502-TNF targeted the tumor cells specifically with stable expression of TNF, which produced a killing effect on tumor cells by regulating the apoptotic signaling pathway. CONCLUSION: Recombinant adenovirus SG502-TNF possessed significant killing effect on TE-1 cells either in vivo or in vitro. This finding demonstrated the potential clinical application of adenovirus SG502.

The attenuation of lung ischemia reperfusion injury by oxymatrine.

To investigate the protective effects of oxymatrine (OMT) on lung ischemia reperfusion injury (LIRI) in rabbits, models of LIRI in rabbit were used. Thirty-two rabbits were randomly divided into four groups: control group (n = 8), ischemia reperfusion group (I/R group, n = 8), OMTl group (n = 8), OMT2 group (n = 8). Lung tissue samples were collected at 40, 80, 120 min time-points after lung ischemia reperfusion. TNF-α, 1I-8, IL-10, apoptosis index (AI), and index of quantitative assessment of histologic lung injury (IQA) were measured in each group. TNF-α and IL-8 in I/R group were significantly higher than those of the control group and OMT2 group (P < 0.01), but in OMT2 group they were significantly lower than those of OMTl group (P < 0.05). IL-10 in OMT2 group and OMTl group was significantly higher than that of I/R group (P < 0.01). But in OMTl group it was significantly lower than that of OMT2 group (P < 0.05). AI in I/R group was significantly higher than that of OMT2 group and the control group at 80 min after lung ischemia reperfusion (P < 0.01). IQA in OMTl group and OMT2 group was significantly lower than that of the I/R group (P < 0.01). Oxymatrine can protect against LIRI in rabbits by upregulating levels of IL-10 and downregulating levels of TNF-α and IL-8, inhibiting the alveolar cells apoptosis and inflammatory response, and attenuating the acute LIRI.

Anti-tumor effects of gene therapy with GALV membrane fusion glycoprotein in lung adenocarcinoma.

This study examined the efficacy of gene therapy of lung adenocarcinoma using specifically controlled type I herpes simplex virus recombinant vector expressing Gibbon ape leukemia virus membrane fusion glycoprotein gene (GALV.fus). Recombinant HSV-I plasmid carrying target transgene was constructed, and recombinant viral vector was generated in Vero cells using Lipofectamine transfection. Viral vector was introduced into lung adenocarcinoma A549 cells or human fetal fibroblast HFL-I GNHu 5 cells, or inoculated into human lung adenocarcinoma xenografts in nude mice. The anti-tumor and cytotoxic effects of GALV-FMG, the transgene, were examined in these cell and animal models. Expression of GALV-FMG in xenographs achieved 100 % tumorigenicity. Recombinant HSV-I viral vector also exhibited significant tumor cell killing effect in vitro. Relative survival rates of tumor cells treated with GALV-FMG or control vectors were, respectively, 20 and 70 %. GALV.fus has a potent anti-tumor effect against lung cancer both in vitro and in vivo. This anti-tumor potential provides foundation for further studies with this vector.

Gene therapy of lung adenocarcinoma using herpes virus expressing a fusogenic membrane glycoprotein.

The aim of this study is to observe the in vitro-targeted destruction of lung adenocarcinoma using recombinant Type I herpes simplex virus (HSV-I)-mediated gibbon ape leukemia virus envelope glycoprotein (GALV.fus), controlled by UL38 promoter and cytomegalovirus promoter (CMVP). A recombinant HSV-I plasmid encoding the GALV.fus was transfected into green monkey kidney cells, the lung adenocarcinoma line A549, and the human fetal fibroblast cell line HFL-I GNHu5 in various doses. The effects and expression of in vitro GALV.fus were observed using an inverted microscope. Enhanced green fluorescence protein expression served as the contro1 for GALV.fus. Recombinant HSV-I virus was produced. Fusogenic recombinant virus infection led to cell fusions in A549 in a dose-dependent manner. Nonfusogenic viruses only produced conventional cytotoxic effects. Recombinant HSV-I with the CMVP initiated cell fusions in HFL-1 GNHu5 cells with arrested cell cycles or as quiescence. HSV-I regulated by UL38p caused cell fusion only in growing cells. Protein expression of GALV.fus was confirmed by Western Blot in infected A549 and HFL-1 GNHu5. Delivery and tumor-specific expression of GALV.fus gene can selectively and safely target lung cancer in vitro, and may prove to be a novel gene therapy for lung cancer.

[The construction of recombinant type I herpes simplex virus carrying GALV.fus gene and its antitumor effect in nude mice].

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.