Surgical treatment of severe benign tracheal stenosis.

OBJECTIVE: To present clinical experiences regarding surgical treatment of patients with severe cicatricial tracheal stenosis. PATIENTS AND METHODS: From January 2008 to March 2020, 14 patients underwent tracheal resection and reconstruction under general anesthesia. Nine cases had cervical tracheal stenosis and five cases had thoracic tracheal stenosis. The mean diameter and length of strictured trachea was 0 - 8 mm with a mean of 4.5 ± 2.4 mm and 1 - 3 cm with a mean of 1.67 ± 0.63 cm, respectively. General anesthesia and mechanical ventilation were performed in ten cases and four patients underwent femoral arteriovenous bypass surgery due to severe stenosis. End-to-end anastomosis of trachea was performed in 13 cases and the anastomosis between trachea and cricothyroid membrane was performed in one case. Absorbable and unabsorbable sutures were used for the anterior and posterior anastomoses, respectively. Postoperative neck anteflexion was maintained by a suture between the chin and superior chest wall. The relevant data of the 14 patients were retrospectively reviewed, and the operation time, blood loss, postoperative hospital stay, postoperative complications and follow-up were retrieved. RESULTS: There was no intraoperative death. The length of resected trachea ranged from 1.5 to 4.5 cm with a mean of 1.67 ± 0.63 cm. Operation time ranged from 50 - 450 min with a mean of 142.8 ± 96.6 min and intraoperative hemorrhage ranged from 10 - 300 ml with a mean of 87.8 ± 83.6 ml. Follow-up period ranged from 5 to 43 months with a mean of 17.9 ± 10.6 months. None of the patients had recurrent laryngeal nerve paralysis during postoperative follow-up. Ten cases were discharged uneventfully. Anastomosis stenosis occurred in three cases who received interventional therapies. Bronchopleurocutaneous fistula occurred in one patient after 6 days postoperatively and further treatment was declined. CONCLUSION: The strategies of anesthesia, mechanical ventilation, identification of stenosis lesion, the "hybrid" sutures and postoperative anteflexion are critical to be optimized for successful postoperative recovery.

Multi-center experience in an optimized right upper lobectomy surgical procedure in China.

BACKGROUND: This multi-center study was aimed at retrospectively evaluating the feasibility, safety, clinical outcomes, and surgical learning curve of an optimized procedure for right upper lobectomy (RUL), which is challenging because of the anatomical structures and features of this lobe. METHODS: This study included 45 RUL cases of robot-assisted thoracoscopy (RATS) in a pilot cohort and 187 RUL cases of video-assisted thoracoscopy (VATS) in three cohorts. A total of 121 and 111 patients underwent traditional and optimized RUL, respectively. The optimized surgical procedure was performed to consecutively transect the superior arterial trunk and bronchus, and finally disconnect the pulmonary vein and posterior ascending artery with interlobar fissures. Clinical and radiological data were reviewed retrospectively. RESULTS: Optimized RUL can be performed successfully by RATS or VATS. The optimized procedure yielded better clinical outcomes than the traditional procedure, including shorter operation times, less blood loss, fewer complications, shorter hospital times, lower costs, and a lower likelihood of postoperative intermedius bronchial kinking. Additionally, for calcified interlobar lymph nodes, the optimized VATS group was less likely to be converted to thoracotomy than the traditional group. The skills required to perform optimized VATS RUL can be gained by surgeons after 12 to 15 cases. The two RUL procedures in the pilot cohort showed similar disease-free survival. CONCLUSIONS: The optimized RUL was safe, economical, and feasible, with a short learning curve and satisfactory disease-free survival.

Analysis of the unplanned reoperation following surgical treatment of pulmonary tumor.

BACKGROUND: In this study, we aimed to summarize the extremely important lesson and experience in the whole process of surgical treatments of lung tumors for the benefit of steps taken to prevent against unplanned reoperation. METHODS: Demographical and clinical information of 7732 patients were retrospectively retrieved and reviewed, who were diagnosed with pulmonary tumor and underwent surgical treatments from January 2016 to March 2021. Those patients who underwent unplanned reoperation for the treatment of severe complications were focused carefully and analyzed meticulously. RESULTS: A total of forty-one patients (41/7732) received 44 unplanned reoperations. Among them, eight and thirty-three patients were diagnosed with benign and malignant tumor, respectively. The incidence of unplanned reoperations seemed to be similar on both sides (Left vs. Right: 12/3231 vs. 29/4501, p = 0.103). Lobectomy plus segmentectomy is prone to reoperation (2/16, 12.5%) as compared to the other types of surgery. The complications leading to reoperation was hemothorax, including active hemorrhage (23/44, 52.3%) and clotted hemothorax (6/44, 13.6%), chylothorax (8/44, 18.2%), and the others (7/44, 15.9%) including bronchopleural fistula, torsion, or injury of right middle bronchus and pulmonary bulla rupture. The morbidity and mortality after unplanned reoperation were 17.1% (7/41) and 12.2% (5/41), respectively. CONCLUSIONS: Bronchi or vessel stumps, the surgical edges of the lung parenchyma, and pleural adhesions should be checked to avoid postoperative bleeding. Prophylactic ligation of the thoracic duct should be recommended in case of the suspected oily-like exudation in the lymph node bed. Smooth expansion of the middle lobe is important to avoid narrowing and torsion before transection of the bronchus.

The miR-23a/27a/24-2 cluster promotes postoperative progression of early-stage non-small cell lung cancer.

Even with optimal surgery, many early-stage non-small cell lung cancer (NSCLC) patients die of recurrence. Unfortunately, there are no precise predictors for postoperative recurrence in early-stage NSCLC, and the recurrence mechanism is still unclear. In this study, we found that simultaneous overexpression of all miRNAs in the miR-23a/27a/24-2 cluster was closely associated with postoperative recurrence, ß-catenin upregulation and promoter methylation of p16 and CDH13 in early-stage NSCLC patients. In addition, in vitro and in vivo experiments show that overexpression or inhibition of all miRNAs in the miR-23a/27a/24-2 cluster significantly stimulated or inhibited NSCLC cell stemness, tumorigenicity and metastasis. Furthermore, we demonstrated that the miR-23a/27a/24-2 cluster miRNAs activated Wnt/ß-catenin signaling by targeting their suppressors and stimulated promoter methylation-induced silencing of p16 and CDH13 by affecting DNA methylation-related genes expression. Our findings suggest that simultaneous high expression of all miRNAs in the miR-23a/27a/24-2 cluster represents a new biomarker for predicting postoperative recurrence in early-stage NSCLC. The miR-23a/27a/24-2 cluster miRNAs stimulate early-stage NSCLC progression through simultaneously stimulating Wnt/ß-catenin signaling, and promoter methylation-induced tumor suppressor genes silencing. In addition, simultaneous inhibition of all miRNAs in the miR-23a/27a/24-2 cluster may be a useful strategy for treatment of early-stage NSCLC recurrence.

The Human Positive Cofactor 4 is a Promising Chemotherapeutic Target in Lung Adenocarcinoma.

Reduced sensitivity to chemotherapeutic drugs is almost inevitable in lung adenocarcinoma patients. Thus, understanding the relevant mechanisms is urgent. Positive cofactor 4 (PC4) was at first revealed to be a coactivator of basal transcription. Previous research has shown that PC4 participates in various cellular processes in normal and malignant cells. However, it is still unknown whether PC4 participates in altering the lung adenocarcinoma cell sensitivity to chemotherapy, and the relevant mechanisms remain to be explained. In this study, we discovered that PC4 was overexpressed in cisplatin-resistant lung adenocarcinoma cells. PC4 decreased cisplatin's cytotoxic effects on lung adenocarcinoma in vivo and in vitro. Furthermore, PC4 positively correlated with SOX9 in multiple cancers. PC4 was an upstream regulator of SOX9 in lung adenocarcinoma. Furthermore, PC4 mediated lung adenocarcinoma cell sensitivity to the HIF-PH inhibitor DMOG and the mTOR inhibitor rapamycin, and PC4 mediated the synergistic effect of DMOG and cisplatin. Finally, PC4 destabilized HIF-1α upon cisplatin treatment. Our research showed that PC4 participates in mediating lung adenocarcinoma cell sensitivity to multiple drugs. Mechanistically, PC4 governs multiple downstream pathways associated with chemotherapy resistance, including the SOX9 and HIF-1α pathways. Thus, PC4 is a promising chemotherapeutic target in lung adenocarcinoma.

Ternary supramolecular nanocomplexes for superior anticancer efficacy of natural medicines.

The discovery of effective anticancer drug delivery systems and elucidation of the mechanism are enormous challenges. Using two drug administration-approved biomaterials, we constructed a natural medicine (NM)-loaded ternary supramolecular nanocomplex (TSN) suitable for large-scale production. The TSN has a better effect against cancer cells/stem cells than NM with differentially upregulated (27 versus 59) and downregulated (165 versus 66) proteins, respectively. Treatment with the TSN induced apoptosis and G2/M arrest, inhibited cell proliferation, metastasis and invasion, reduced colony/sphere formation, and decreased the frequency of side population cells and CD133+CD44+ABCG2+ cells. These results were revealed by multiple analyses (proteomic analysis, transwell migration and colony/sphere formation assays, biomarker profiling, etc.). We first reported the proteomic analysis of small lung cancer cells responding to a drug or its nanovesicles. We first conducted a proteomic evaluation of tumor cells responding to a drug supramolecular nanosystem. The supramolecular conformation of the TSN and the interactions of the TSN with albumin were verified by molecular docking experiments. The dominant binding forces in the TSN complexation process were electrostatic interactions, van der Waalsinteractions and bond stretching. The TSN binds to albumin more readily than NM does. The TSN has good in situ absorptive and in vitro/vivo kinetic properties. The relative bioavailability of the TSN to EA was 458.39%. The NM-loaded TSN is a supramolecular vesicle that can be produced at an industrial scale for efficient cancer therapy.

BCAR1 plays critical roles in the formation and immunoevasion of invasive circulating tumor cells in lung adenocarcinoma.

Background: We investigated the roles of breast cancer anti-estrogen resistance 1 (BCAR1/p130Cas) in the formation and immunoevasion of invasive circulating tumor cells (CTCs) in lung adenocarcinoma (LUAD). Methods: Biomarkers of CTCs including BCAR1 and CD274, were evaluated by the CanPatrol method. Proteomics analysis of LUAD cells and exosomes after BCAR1 overexpression (BCAR1-OE) was performed by mass spectrometry. Cell functions and relevant signaling pathways were investigated after BCAR1 knockdown (BCAR1-KO) or BCAR1-OE in LUAD cells. Lastly, in vitro and in vivo experiments were performed to confirm the roles of BCAR1 in the formation and immunoevasion of CTCs. Results: High expression of BCAR1 by CTCs correlated with CD274 expression and epithelial-to-mesenchymal transition (EMT). RAC1, together with BCAR1, was found to play an important role in the carcinogenesis of LUAD. RAC1 functioned with BCAR1 to induce EMT and to enhance cell proliferation, colony formation, cell invasion and migration, and anoikis resistance in LUAD cells. BCAR1 up-regulated CD274 expression probably by shuttling the short isoform of BRD4 (BRD4-S) into the nucleus. CTCs, as well as tumor formation, were prohibited in nude mice xenografted with BCAR1-KO cells. The co-expression of BCAR1/RAC1 and BCAR1/CD274 was confirmed in LUAD. BCAR1 expression in LUAD is an indicator of poor prognosis, and it associates with immunoevasion. Conclusion: BCAR1, as a new target for the treatment of LUAD, plays roles in the formation and immunoevasion of invasive CTCs. The mechanism includes triggering EMT via RAC1 signaling and up-regulating CD274 expression by shuttling BRD4-S into the nucleus.

Circulating tumor cells with epithelial-mesenchymal transition markers as potential biomarkers for the diagnosis of lung cancer.

BACKGROUND: Circulating tumor cells (CTCs) can be clustered into three subtypes according to epithelial-mesenchymal transition (EMT) markers: CTCs with epithelial markers (E-CTCs), CTCs with mesenchymal markers (M-CTCs), and CTCs with both markers (E&M-CTCs). CTC detection has clinical implications in the diagnosis of lung cancer (LC). AIM: To clarify the diagnostic value of CTCs categorized by EMT markers in LC. METHODS: The study included 106 patients with lung adenocarcinoma, including 42 ground-glass opacities (GGO) and 64 solid lesions, who underwent surgery between July 2015 and December 2019. Eleven patients with benign tumors and seventeen healthy controls were included. CTCs in peripheral blood and associated EMT markers were detected preoperatively using the CanPatrolTM technique. The diagnostic power of CTCs for discriminating LC cases from controls was analyzed by the receiver operating characteristic (ROC) curve. The CytoploRare technique was used in 20 cases and 18 controls for validation, and Kappa values were calculated to evaluate consistency between techniques. RESULTS: Of the 106 LC cases, 94 (89.6%) had at least one CTC. CTCs were detectable in 35 (83.3%) of 42 GGO cases. Total CTCs and E&M-CTCs were significantly more frequent in LC cases than in benign or healthy controls. The proportion of M-CTCs plus E&M-CTCs increased gradually from healthy controls, to benign controls, to LC cases. The area under the ROC curve of total CTCs and E&M-CTCs was > 0.8 and > 10.75, respectively. The combined sensitivity of total-CTCs and E&M-CTCs was 85.85% for LC patients (80.95% for GGO patients) and the specificity was 78.57%. The Kappa value was 0.415, indicating relative consistency between CanPatrolTM and CytoploRare. CONCLUSION: CTC detection is valuable for distinguishing LC from controls, and particularly E&M-CTC detection warrants further study.

GRP75-mediated upregulation of HMGA1 stimulates stage I lung adenocarcinoma progression by activating JNK/c-JUN signaling.

BACKGROUND: Recurrence is a major challenge in early-stage lung adenocarcinoma (LUAD) treatment. Here, we investigated the role and mechanism of high-mobility group AT-hook 1 (HMGA1) and glucose-regulated protein 75-kDa (GRP75) in stage I LUAD and evaluated their potential as biomarkers for predicting the recurrence and prognosis of stage I LUAD. METHODS: The TCGA dataset was used to investigate the clinical significance of HMGA1 and GRP75 in early-stage LUAD. The biological functions of HMGA1 and GRP75 in LUAD were investigated both in vitro and in vivo through overexpression and knockdown experiments. The interaction and regulation between HMGA1 and GRP75 were evaluated with coimmunoprecipitation and ubiquitination assays. The downstream signaling pathway of the GRP75/HMGA1 axis was investigated by mRNA-sequencing analysis. RESULTS: Both HMGA1 expression levels and GRP75 expression levels were associated with recurrence in stage I LUAD patients. In particular, HMGA1 had potential as an independent prognostic factor in stage I LUAD patients. Overexpression of GRP75 or HMGA1 significantly stimulated LUAD cell growth and metastasis, while silencing GRP75 or HMGA1 inhibited LUAD cell growth and metastasis in vitro and in vivo. Importantly, GRP75 inhibited ubiquitination-mediated HMGA1 degradation by directly binding to HMGA1, thereby causes HMGA1 upregulation in LUAD. In addition, the GRP75/HMGA1 axis played its role by activating JNK/c-JUN signaling in LUAD. CONCLUSIONS: The activation of GRP75/HMGA1/JNK/c-JUN signaling is an important mechanism that promotes the progression of stage I LUAD, and a high level of HMGA1 is a novel biomarker for predicting recurrence and a poor prognosis in stage I LUAD patients.

Risk factors of conversion in robotic- and video-assisted pulmonary surgery for non-small cell lung cancer.

BACKGROUND: This study aimed to investigate risk factors of conversion to thoracotomy for patients with non-small cell lung cancer (NSCLC) underwent robotic- (RATS) or video-assisted thoracoscopic surgery (VATS). METHODS: A retrospective review was conducted to included consecutive participants from January 2016 to December 2018. Three groups [mini-invasive, conversion, and up-front open thoracotomy (OT) groups] and two series of comparison (conversion versus mini-invasive, and conversion versus OT) were generated. Propensity score-matched analysis (1:1) was conducted to verify outcomes of complications and perioperative factors. Multivariate binary logistic regression analysis was used to identify potential risk factors of conversion. RESULTS: 1177 patients (912 in mini-invasive group, 180 in conversion group, and 85 in OT group) were included. The overall conversion rate was 16.5%. Robotic approach resulted in dramatically lower conversion rate compared to VATS (2.4% vs 25.1%, p < 0.001). After propensity adjustment, no significant difference of complication rates was identified when comparing conversion group with mini-invasive and OT groups. Multivariate regression analyses shown that robotic approach (odd ratio (OR) = 0.037, 95% confidential interval (CI) 0.016-0.087), tumor size < 5 cm (OR = 0.274, 95% CI 0.152-0.493), no chief symptom(OR = 0.311, 95% CI 0.178-0.545), body mass index < 25 kg/m2 (OR = 0.537, 95% CI 0.343-0.842), and lobectomy (OR = 0.079, 95% CI 0.017-0.370) were independent protectors of conversion. CONCLUSIONS: Seven demographic factors might be recognized as independent predictors of conversion. For patients with highly risk of conversion, robotic approach is recommended to perform mini-invasive pulmonary surgery over VATS.

Cost-effectiveness evaluation of robotic-assisted thoracoscopic surgery versus open thoracotomy and video-assisted thoracoscopic surgery for operable non-small cell lung cancer.

BACKGROUND: This study aimed to evaluate the cost-effectiveness of robotic-assisted thoracoscopic surgery (RATS) over open thoracotomy (OT) and video-assisted thoracoscopic surgery (VATS) for operable non-small cell lung cancer (NSCLC) from the perspective of Chinese healthcare payer. METHODS: The Markov decision model was developed to assess the 5-year costs and quality-adjusted life year (QALY) of RATS versus OT and VATS for operable NSCLC patients. The propensity-matched cohorts were generated from our clinical center to determine the surgical costs and complication rates. An individual patient data meta-analysis was conducted to estimate model probabilities of progression and survival risks. Other model inputs were abstracted from available studies. The primary outcome was incremental cost-effectiveness ratios (ICERs). RESULTS: RATS contributed to an incremental 0.28 QALYs at an additional cost of $3,104.82, making for an ICER of $10,967.41 per QALY versus OT. Robotic approach harvested an incremental 0.05 QALYs at an additional cost of $4006.86, making for an ICER of $80324.98 per QALY over VATS. RATS shown a same cost-effectiveness probability (0.50) versus OT and VATS at a willing-to-pay (WTP) threshold of $12,000 per QALY and $75,800 per QALY, respectively. The probabilities of cost-effectiveness for RATS were 0.64 and 0.21 at a presupposed WTP threshold of $ 30,000 per QALY versus OT and VATS, respectively. CONCLUSIONS: RATS was evaluated to be cost-effective versus OT for patients with operable NSCLC from the perspective of Chinese healthcare payer. To the contrary, robotic approach was associated with less cost-effective than VATS.

FOXO1 and FOXO3a sensitize non-small-cell lung cancer cells to cisplatin-induced apoptosis independent of Bim.

Low sensitivity to chemotherapy has been a major challenge in the treatment of non-small-cell lung cancer (NSCLC). It is of great clinical significance to discover its mechanisms to improve cell sensitivity to chemotherapeutic drugs. The forkhead box subfamily O (FOXO) transcriptional factors are downstream factors of the phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) pathway and are reported to play pro-apoptotic roles in a variety of cells including NSCLC cells. But their roles and mechanisms in mediating cell response to chemotherapy remain to be discovered. We proposed that FOXO1 and FOXO3a may increase the sensitivity of NSCLC cells to cisplatin. Moreover, we presumed that LY294002, an inhibitor of the PI3K/AKT pathway, may enhance the cytotoxic effects of cisplatin through upregulating FOXO1 and FOXO3a. In the present study, we found that cisplatin initially increased the expressions and nuclear accumulation of FOXO1 and FOXO3a in NSCLC. Knockdown of FOXO1 and FOXO3a significantly decreased the cell sensitivity to cisplatin in vitro and in vivo. Moreover, inhibition of FOXO1 and FOXO3a attenuated cisplatin-induced cell apoptosis independent of Bim, a pro-apoptotic protein downstream of the FOXOs. Moreover, LY294002 synergistically increased the cytotoxic effects of cisplatin. Mechanistically, LY294002 increased the expressions and nuclear accumulation of FOXO1 and FOXO3a. Knockdown of FOXO1 and FOXO3a abrogated the enhancing effect of LY294002 on cisplatin. Taken together, our results suggested that FOXO1 and FOXO3a sensitize NSCLC cells to cisplatin and mediate the enhancing effects of LY294002 on cisplatin.

Is the presence of lung injury in COVID-19 an independent risk factor for secondary lung cancer?

The morbidity and mortality of lung cancer are increasing. The Corona Virus Disease 2019 (COVID-19) is caused by novel coronavirus 2019-nCoV-2, leading to subsequent pulmonary interstitial fibrosis with chronic inflammatory changes, e.g., inflammatory factors repeatedly continuously stimulating and attacking the alveolar epithelial cells. Meanwhile, 2019-nCoV-2 can activate PI3K/Akt and ERK signaling pathways, which can play the double roles as both anti-inflammatory and carcinogenic factors. Moreover, hypoxemia may be developed, resulting in the up-regulation of HIF-1 α expression, which can be involved in the occurrence, angiogenesis, invasion and metastasis of lung cancer. Additionally, the immune system in 2019-nCoV-2 infected cases can be suppressed to cause tumor immune evasion. Therefore, we speculate that COVID-19 may be a risk factor of secondary lung cancer.

Genomic profiles and transcriptomic microenvironments in 2 patients with synchronous lung adenocarcinoma and lung squamous cell carcinoma: a case report.

BACKGROUND: Multifocal lung cancers (MLCs) are common in patients newly diagnosed with lung cancer, and histological results of most synchronous MLCs are similar. Few cases with different histology findings have been reported, and no genomic or transcriptomic profiling of this kind of cases were done before. Here, we analyzed genomic and transcriptomic profiles of all lung tumors from 2 patients with synchronous adenocarcinoma and squamous cell carcinoma in the same lung lobe. CASE PRESENTATION: Two patients were diagnosed as synchronous adenocarcinoma and squamous cell carcinoma and underwent surgical resection. All 4 tumors showed distinct genomic profiles, therefore were independent primary tumors. Several cancer-associated pathways, such as RTK-RAS pathway and Notch pathway, exhibited different mutated genes in different tumors from the same patient. Several known cancer genes with different mutations, including TP53 and KEAP1, were also detected. Mutation signature analysis demonstrated that the tumor initiation might be related to the transcription coupled nucleotide excision repair process. Two tumors for these 2 patients had loss of heterogeneity (LOH) in HLA genes, showing tumor escaping mechanism. Furthermore, tumor microenvironments showed different patterns in 2 tumors from the same patient. The tumor with more neoantigens and no HLA LOH showed more infiltrating CD8+ T cells and more clonal TCRs, indicating a more active microenvironment. CONCLUSIONS: The lung squamous cell carcinoma and lung adenocarcinoma form the same patient are from independent origins. The genetic profiles and transcriptomic microenvironments are quite different for these 2 tumors. With the same genetic background, the 2 tumors in one patient exhibited different tumor escape mechanisms and immune responses, including HLA LOH and T cell infiltrating and expansion.

Short-term effects of Da Vinci robot Nissen fundoplication in the treatment of refractory gastroesophageal reflux disease / 中国胸心血管外科临床杂志

@#Objective    To investigate the short-term effects of Da Vinci robot-assisted Nissen fundoplication in the treatment of refractory gastroesophageal reflux disease (rGERD), and to evaluate the safety and efficacy of its surgical treatment. Methods    A total of 40 patients with rGERD treated by Da Vinci robot-assisted surgery from October 2016 to November 2019 in our hospital were collected. There were 23 males and 17 females at age of 34-76 (61±23) years. The related clinical data were retrospectively analyzed, and the operation skills of Da Vinci robot-assisted Nissen fundoplication with rGERD were summarized. Results    There was no perioperative death or serious complication such as esophagogastric fistula. Postoperative reflux symptoms were significantly improved. DeMeester scores after surgery (39.79±35.01 points vs. 2.61±2.40 points, P=0.029), lower esophageal sphincter pressure (8.74±7.21 mm Hg vs. 24.56±8.76 mm Hg, P=0.020), integrated relaxation pressure (7.29±7.21 mm Hg vs. 16.49±9.99 mm Hg, P=0.023), distal contractile integral (600.49 ± 665.30 mm Hg·s·m vs. 510.99 ± 580.60 mm Hg·s·m, P=0.042), GERD-Q scale score (12.98±2.39 points vs. 7.59±1.11 points, P=0.033) were significantly improved compared with those before surgery. Postoperative dysphagia was found in 2 patients. And dysphagia was alleviated after diet adjustment and other treatments. Conclusion    Da Vinci robot-assisted Nissen fundoplication is a safe and effective treatment for rGERD.

Experience of robot-assisted lung segmentectomy through anterior approach / 中国胸心血管外科临床杂志

@#Objective    To evaluate the feasibility and clinical value of robot-assisted lung segmentectomy through anterior approach. Methods    We retrospectively analyzed the clinical data of 77 patients who underwent robotic lung segmentectomy through anterior approach in our hospital between June 2018 to October 2019. There were 22 males and 55 females, aged 53 (30-71) years. Patients' symptoms, general conditions, preoperative imaging data, distribution of resected lung segments, operation time, bleeding volume, number of lymph node dissected, postoperative duration of chest tube insertion, drainage volume, postoperative hospital stay, postoperative complications, perioperative death and other indicators were analyzed. Results    All operations were successfully completed. There was no conversion to thoracotomy, serious complications or perioperative death. The postoperative pathology revealed early lung cancer in 48 patients, and benign tumors in 29 patients. The mean clinical parameters were following: the robot Docking time 1-30 (M=4) min, the operation time 30-170 (M=76) min, the blood loss 20-400 (M=30) mL, the drainage tube time 2-15 (M=4) days, the drainage fluid volume 200-3 980 (M=780) mL and the postoperative hospital time 3-19 (M=7) days. Conclusion    Robotic lung segmentectomy through anterior approach is a safe and convenient operation method for pulmonary nodules.

CCR7 promote lymph node metastasis via regulating VEGF-C/D-R3 pathway in lung adenocarcinoma.

Lymph node metastasis is still an important issue in metastatic process of lung adenocarcinoma. C-C chemokine receptor 7 (CCR7) has been proved to be closely associated with the metastasis of lung adenocarcinoma, and the mechanism is poorly understood. In order to investigate the relationship between CCR7 and lymph node metastasis in lung adenocarcinoma, and to explore the role of CCR7 in treating lung adenocarcinoma, 40 clinical specimens were collected to define the relationship between CCR7 and lymph node metastasis in lung adenocarcinoma by immunohistochemistry. The siRNA was used to suppress CCR7 expression in A549 cells. The scratch test, transwell test, qRT-PCR, western blot, flow cytometry and immunofluorescence were used to investigate the lymph node metastasis-related function of CCR7 in vitro. The athymic mice subcutaneous injection was used to research lung adenocarcinoma formation in vivo. Clinical case studies show that higher expression of CCR7 in lung adenocarcinoma tissues was associated with a higher lymph node metastasis. Inhibition of expression of CCR7 can reduce the migration and invasion and suppress the expression of VEGF-C, VEGF-D and VEGF-R3 in vitro and in vivo. Moreover, CCR7 silence also suppressed WNT and p-ERK pathways in vitro. All the results indicate that CCR7 can promote lymph node metastasis in lung adenocarcinoma by regulating VEGF-C/D-R3 pathway. Thus CCR7 is proposed to be a potential prediction for poor prognosis of lung adenocarcinoma, and a therapeutic target for lymph node metastasis.

Surgery combined with adenoviral p53 gene therapy for treatment of non-small cell lung cancer: a phase II study.

OBJECTIVE: To assess the efficacy of radical surgery combined with recombinant adenoviral human p53 (rAd-p53) gene therapy in treatment of resectable non-small cell lung cancer. METHOD: A total of 163 patients with resectable NSCLC meeting the inclusion criteria were randomly assigned to two groups: radical surgery alone (S) and radical surgery plus surgical wound surface injection of 2 x 1012 rAd-p53 units (SP). All patients were followed up for at least 3 years for efficacy and safety. Study endpoints were loco-regional recurrence or distant metastasis (Rec-Met) rate as primary endpoints, and progression free survival (PFS), overall survival (OS) and safety assessments as secondary endpoints. RESULTS: Recurrence or metastasis (Rec/Met) after surgery were 24/82 (29.27%) in SP group and 37/81 (45.68%) in S group. The difference in the Rec/Met rate was statistically significant (p = 0.0304) by chi-square test. The hazard ratios after adjusting of age and disease stage (S vs. SP) of PFS and OS are 1.772 (95% CI, 1.102 to 2.848) and 2.047 (95% CI, 1.109 to 3.377), respectively. The 3 years PFS and OS for SP vs. S were 71.9% vs. 46.9%, and 88.4% vs. 67.0%, respectively. Differences in PFS and OS between two treatment groups were significant with the p values of 0.0165 and 0.0191, respectively, using Log-Rank test. CONCLUSIONS: The wound surface injection of rAd-p53 showed efficacious effects in preventing recurrence or metastasis and improving PFS and OS after a radical surgery in patients with NSCLC.

PC4 induces lymphangiogenesis dependent VEGF-C/VEGF-D/VEGFR-3 axis activation in lung adenocarcinoma.

Human transcriptional positive cofactor 4 (PC4) is a novel marker for diagnosis and treatment of advanced human cancers metastasis. In human lung adenocarcinoma, tumor lymphangiogenesis, an important early event, can promotes lymphatic metastasis, while it has been reported that VEGF-C/VEGF-D/VEGFR-3 axis plays an important role in lymphangiogenesis. The proposed study aims to explore whether PC4 correlates with VEGF-C/VEGF-D/VEGFR-3 axis of lymphangiogenesis in the lymph node metastasis during lung adenocarcinoma. Here, small interfering RNA technique was employed to investigate the relationship of PC4 and the VEGF-C/VEGF-D/VEGFR-3 axis in lung adenocarcinoma cell lines as well as tumor xenografts of mice model. And then mRNA and protein levels of PC4, VEGF-C, VEGF-D and VEGFR-3 were analyzed. Moreover, the correlation between PC4 expression and lymphatic vessel density or the rate of metastatsis in vivo was also revealed. Down-regulating PC4 expression resulted in the lower expression of VEGFC, VEGF-D and VEGFR-3 in mRNA and protein levels, and PC4 expression was significantly related with the factor of VEGF-C/VEGF-D/VEGFR-3 axis expression (P<0.05). Meanwhile, high expression level of PC4 was accompanied by the higher density of tumor lymphatic vessels and the rate of metastatsis in vivo (P<0.05). PC4 expression correlated with the levels of VEGF-C, VEGF-D and VEGFR-3 during the development of lymphangiogenesis and lymphatic metastasis in lung adenocarcinoma in vitro and in vivo, which may be a novel marker in the development of lymphangiogenesis and lymphatic metastasis of tumors.