Comparison of indocyanine green-near-infrared fluorescence guided and traditional mediastinal lymphadenectomy during radical esophagectomy: A randomized controlled trial.

BACKGROUND: The extent of lymph node dissection during radical esophagectomy remains a controversial topic. Thus, this study mainly aimed to explore the location of sentinel lymph nodes in esophageal squamous cell carcinoma and the application value of the indocyanine green-near-infrared fluorescence system in lymphadenectomy. METHODS: This randomized controlled clinical trial (ClinicalTrials.gov, NCT04615806) included 42 participants without neoadjuvant therapy who were lymph node negative based on positron emission tomography/computed tomography findings. Traditional esophagectomy with indocyanine green-near-infrared fluorescence imaging was performed after injecting 0.5 mL indocyanine green (1.25 mg/mL) into the esophageal submucosa in the 4 peritumoral quadrants. The primary endpoint was to determine the location of the sentinel lymph node in esophageal squamous cell carcinoma based on postoperative pathologic reports. RESULTS: A total of 40 patients, with 20 in each group, were included in the final analysis. In the indocyanine green group, indocyanine green-near-infrared fluorescence imaging was successful in all subjects. Seven cases (cases 2, 3, 9, 11, 17, 18, and 20) in the indocyanine green group exhibited lymph node metastases, all of which were near-infrared positive. The detection rate, positive predictive value, negative predictive value, sensitivity, and specificity were 100% (20 of 20 cases), 8.7% (13/150), 100% (265/265), 100% (13/13), and 65.9% (265/402), respectively. All near-infrared-negative lymph nodes were nonmetastatic lymph nodes. In addition, the number of mediastinal lymph nodes resected in the indocyanine green group was significantly higher than in the non-indocyanine green group. CONCLUSION: Indocyanine green-near-infrared might be an important and promising technique in predicting sentinel lymph nodes of esophageal squamous cell carcinoma and could significantly improve the detection rate of lymph nodes of esophageal squamous cell carcinoma.

miR-1301-3p promotes invasion and migration and EMT progression in esophageal cancer by downregulating NBL1 expression.

BACKGROUND: Esophageal cancer (ESCA) is one of the most aggressive and lethal human malignant cancers. MicroRNA-1301-3p (miR-1301-3p) plays vital roles in a majority of malignancies. The aim of this study was to investigate the role of miR-1301-3p/NBL1 axis on ESCA cell invasion, migration, epithelial-mesenchymal transition (EMT) process, as well as its association with prognosis of ESCA patients. METHODS: The expression levels of miR-1301-3p and NBL1 were predicted by bioinformatics and further verified by RT-qPCR assays. Kaplan-Meier (K-M) plotter analysis and univariate and multivariate Cox analyses were used to evaluate the relationship between miR-1301-3p and clinicopathological variables and prognosis. The role of miR-1301-3p on cell invasion, migration was detected by transwell invasion, and wound healing assays, respectively. The EMT-related proteins were detected by western blot. The target genes and the target binding sites were predicted by bioinformatics and further determined by RT-qPCR assay. RESULTS: MiR-1301-3p was remarkably upregulated in ESCA tissues and cells, and its high expression was associated with poor prognosis of ESCA. Overexpression of miR-1301-3p promoted ESCA cell invasion, migration and mediated EMT process in vitro, whereas knockdown of miR-1301-3p showed the opposite effects. Moreover, NBL1 was predicted as a target gene of miR-1301-3p. NBL1 was lowly expressed in ESCA cells and significantly decreased after upregulation of miR-1301-3p. Meanwhile, we found that low expression of NBL1 was significantly associated with poor prognosis of ESCA patients. CONCLUSION: MiR-1301-3p is a potential biomarker for predicting the prognosis of ESCA patients. It may promote ESCA invasion, migration and EMT progression by regulating NBL1 expression.

A novel form of precise segmentectomy-Triumphal arch-like anatomical segmentectomy.

The increasingly accurate sublobar anatomical resection is constantly being explored and practiced. Surgeons try to preserve as much viable lung tissue as possible. Sublobar resection of the target tissue is similar with a cone-shaped structure which penetrates deeply into the pulmonary parenchyma and runs through the lobe at both ends. This has not previously been described. The remaining lung tissue resembles the Triumphal Arch in Paris, France. Here, we describe triumphal arch-like sublobectomy in detail, aiming to provide clinicians with an idea to explore this novel sublobectomy under similar conditions.

How to distinguish thoracic and cervical lymph nodes during minimally invasive esophagectomy.

PURPOSE: In this article, we aimed to reconstruct the cervical-thoracic junction plane (CTJP) using a three-dimensional (3D) reconstruction system. Thus, the CTJP can be judged during surgery to better distinguish cervical-thoracic lymph nodes. METHODS: We included patients in Fujian Medical University Union Hospital from December 2019 to March 2020. All patients underwent a thin-slice and enhanced computed tomography scan of the chest with 3D reconstruction using the IQQA system (EDDA technology) to reconstruct the CTJP, brachiocephalic trunk, right common carotid artery, and right subclavian artery. The distance from the intersection of the right subclavian artery and the CTJP to the origin of the right subclavian artery (ORSA) was measured, and the relationship between this distance and the patient's sex, BMI and height was analyzed. RESULTS: Seventy-three patients were enrolled, of whom 12 had ORSA above the CTJP, while 61 had ORSA below the plane. There was a significant difference in age between the two groups (p = 0.04), compared with height, weight and BMI (p > 0.05). In 61 patients with the ORSA below the CTJP, the average distance was 24.7 ± 7.6 mm. The difference between the distance and BMI (p = 0.02) was statistically significant, and it was increased with increasing BMI. CONCLUSIONS: The relationship between the ORSA and CTJP can be clarified through 3D reconstruction. The cervical-thoracic recurrent laryngeal nerve lymph nodes can be distinguished clearly in minimally invasive esophagectomy, contributing to the accurate N staging of middle-thoracic esophageal cancer.

Cost-effectiveness of osimertinib versus placebo in resected EGFR-mutated non-small cell lung cancer in China.

PURPOSE: We aim to assess whether osimertinib postoperative adjuvant therapy, compared with placebo, is cost-effective in China. METHODS: We set up the Markov model that contains three health states over a 20-year period. Data were collected from the ADAURA trial that included transition probabilities and safety data. Through the analysis of literature and local charges, we explore both the cost and utility values. Sensitivity analyses were employed using TreeAge Pro software to access model stability. FINDINGS: Patients in the osimertinib group had 1.46 more Quality-adjusted Life Years (8.45 QALYs vs 6.99 QALYs) than the placebo group at an incremental cost of $14098.51($39962.99 vs $25864.48). Compared with the placebo group, the treatment strategy with osimertinib postoperative adjuvant therapy had an incremental cost-effectiveness ratio of $9661.97/QALY. The probability of the osimertinib-assisted therapy strategy being cost-effective will reach 100% if the threshold of willingness to pay is above $15,000/QALY. IMPLICATIONS: From the perspective of the Chinese Healthcare System, the treatment strategy with osimertinib postoperative adjuvant therapy is more cost-effective than the placebo strategy.

Pericancerous lymph node imaging with indocyanine green-guided near-infrared fluorescence in radical esophagectomy: Protocol for a single-center, prospective, randomized controlled clinical trial.

INTRODUCTION: The incidence and mortality rates of esophageal carcinoma are higher than those of most malignancies in humans. Radical esophagectomy is the preferred treatment for early-stage esophageal cancer. However, the extent of lymphadenectomy during radical esophagectomy remains controversial. Indocyanine green (ICG) is the most commonly used imaging agent for the diagnosis of tumors and metastatic lymph nodes in clinical settings. Thus, the main aim of this study was to evaluate pericancerous lymph nodes imaging in video-assisted thoracoscopic surgery radical esophagectomy using a near-infrared (NIR) ICG imaging system and to improve the detection rate of sentinel lymph nodes (SLNs) and overall survival of patients with esophageal cancer. METHODS: This was a single-center, prospective, randomized controlled clinical trial (allocation rate = 1:1). Forty treatment-naive esophageal cancer patients were recruited and divided into two groups: the ICG and control groups. The inclusion criteria were age, absence of preoperative neoadjuvant therapy, elective surgery, and signed informed consent. Data of participants at four different time points (preoperation, intraoperation, postoperative 1 week and 3 months) were collected and recorded. The main endpoint of this study was to explore the accuracy and false-negative rate of lymphadenectomy using NIR-ICG fluorescence imaging and to identify the location of esophageal cancer SLN combined with postoperative pathological reports. DISCUSSION: This trial will provide more evidence on the extent of lymph node dissection for esophageal cancer and contribute to the development of treatment guidelines for esophageal cancer. TRIAL REGISTRATION NUMBER: NCT04615806.

A propensity sore-matched study: Applying a modified chest tube drainage strategy in rapid rehabilitation following uni-portal thoracoscopic pulmonary wedge resection.

PURPOSE: This study aimed to compare the value of a modified chest tube drainage strategy to a traditional drainage strategy in single-port thoracoscopic pulmonary wedge resection. METHODS: From January 2019 to July 2021, we collected clinical data on 405 patients who underwent single-port thoracoscopic pulmonary wedge resection in the No.1 Department of Thoracic Surgery at Fujian Medical University Union Hospital, with 121 (29.9%) cases in the modified drainage strategy group and 284 (70.1%) cases in the traditional drainage strategy group. The propensity score matching method (Match Ratio = 1:1) was used to reduce differences in clinical characteristics between the two groups. RESULTS: Following 1:1 propensity score matching, 120 matched pairs (240 patients) were included in the study. There was no significant difference in general clinical characteristics between the two groups. There was no statistical difference in intraoperative factors except for operative times (71.42 ± 22.98 min vs. 86.80 ± 36.75 min, p < 0.001). In terms of postoperative factors, there were significant differences in postoperative chest tube duration (0.00 ± 0.00 h vs. 32.68 ± 18.51 h, p < 0.001), total drainage volume (143.03 ± 118.33 ml vs. 187.73 ± 140.82 ml, p = 0.008), postoperative hospital stay (2.61 ± 0.70 days vs. 3.27 ± 1.88 days, p < 0.001), number of additional pain relief (0.14 ± 0.40 vs. 0.42 ± 0.74, p < 0.001), facial pain score (2.7 ± 1.8 vs. 3.6 ± 2.7, p = 0.005) and adverse events (p = 0.046). Furthermore, there was a statistical difference between the two groups regarding CTCAE grade-1 complication, but no statistical difference in CTCAE grade-2 complication. CONCLUSIONS: A modified drainage strategy in single-port thoracoscopic pulmonary wedge resection is safe and feasible, allowing for less postoperative rehabilitation time, pain relief, reduced postoperative pleural effusion, and reduced clinical workload.

[Comparison of chemical components between aerial and underground parts of Coptis chinensis based on UPLC-Q-TOF-MS~E technology].

The ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS~E) technology was employed to compare the chemical components between the aerial and underground parts of Coptis chinensis samples from different batches. According to the retention time, molecular ion peak, and LC-MS~E fragment information of the reference substances and available literature, we identified a total of 40 components. Thirty-three and 31 compounds were respectively identified in the underground part(taproots) and the aerial part(stems and leaves) of C. chinensis. Among them, 24 compounds, including alkaloids(e.g., berberine and jatrorrhizine) and phenolic acids(e.g., chlorogenic acid, quinic acid, and tanshinol), were common in the two parts. In addition, differential components were also identified, such as magnoline glucoside in the underground part and(±) lariciresionol-4-ß-D-glucopyranoside in the aerial part. The analysis of fragmentation pathways based on spectra of reference substances indicated the differences among samples of different batches. Furthermore, we performed the principal component analysis(PCA) for the peak areas of C. chinensis in different batches. The results showed that the underground part and the aerial part were clearly clustered into two groups, indicating that the chemical components contained in the two parts were different. Furthermore, the results of partial least squares discriminant analysis(PLS-DA) identified 31 differential compounds(VIP value>1) between the underground part and the aerial part, mainly including alkaloids, phenolic acids, lignans, and flavonoids. This study proves that C. chinensis possesses great development potential with multiple available compounds in stems and leaves. Moreover, it sheds light on for the development and utilization of non-medicinal organs of C. chinensis and other Chinese medicinal herbs.

"Split" combined subsegmentectomy: A case series.

BACKGROUND: Clinically, some specific pulmonary nodules have safe resection margins that are located in multiple subsegments in the center of lung lobe. It is therefore difficult to ensure the resection margins through conventional combined subsegmentectomy or wedge resection, and thus lobectomy is required. For these types of pulmonary nodules, "split" operation was performed to fully inflate the reserved lung tissues on both sides. This study aimed to preliminarily assess the feasibility and safety of "split" operation. METHODS: Cases with these types of pulmonary nodules were selected. Some of the cases were subjected to "split" operation and the operation conditions, including operation time, bleeding amount, length of hospital stay, computed tomography (CT) reexaminations, and pulmonary function, were analyzed. RESULTS: The "split" operation was performed and successfully completed for seven patients. There was no case of conversion to thoracotomy and the median operation time, bleeding amount, and length of hospital stay were 219 min, 30.0 ml, and 4 days, respectively. No death or pulmonary complications such as pulmonary infection, lung torsion, and bronchopleural fistula occurred, and only one patient had incision fat liquefaction. After 3 months, the median percentage of preserved pulmonary function was 85.8% and a CT scan showed that the reserved lung tissues of the seven patients were well inflated and without obvious imaging findings of atelectasis. CONCLUSION: "Split" combined subsegmentectomy can be used as a new and safe operative method for deep pulmonary nodules with safe resection margins involving multiple subsegments in the center of the lung lobe.

miR-21-5p is a Biomarker for Predicting Prognosis of Lung Adenocarcinoma by Regulating PIK3R1 Expression.

BACKGROUND: Lung cancer (LUCA) is one of the most prevalent human malignancies, and the leading cause of cancer-related deaths worldwide. Previous reports have shown that miR-21-5p plays a vital role in development of various tumors. Here, we explored the relationship between miR-21-5p/PIK3R1 axis and prognosis of patients with lung adenocarcinoma (LUAD). METHODS: MiRNAseq data, deposited in The Cancer Genome Atlas (TCGA) database, was downloaded and used to determine patterns of miR-21-5p expression in both LUAD and normal lung tissues. Statistical analyses and data visualization were performed using dbDEMC v3.0 platform, starBase v3.0 database and packages implemented in R software. Next, we employed TargetScan Human, miRDB and DIANA Tools databases to predict miR-21-5p target genes, then analyzed their expression patterns as well as prognostic value in LUAD. FINDINGS: Most human cancers overexpressed miR-21-5p. Specifically, miR-21-5p was significantly upregulated in LUAD tissues relative to normal lung tissues (P < 0.001), and this high expression was significantly correlated with poor patient prognosis (hazard ratio [HR]=1.45, P = 0.014). PIK3R1 was predicted as a miR-21-5p target gene, and both were negatively correlated (r=-0.218, P < 0.01). Notably, PIK3R1 was significantly downregulated in LUAD, relative to normal lung tissues (P < 0.01), with its overexpression significantly associated with poor prognosis of LUAD patients (HR = 0.62, P = 0.0014). CONCLUSION: miR-21-5p is a potential prognostic biomarker for LUAD patients. Moreover, it might be playing a role in LUAD progression by regulating PIK3R1 expression.

Effect of Micronization on Panax notoginseng: In Vitro Dissolution and In Vivo Bioavailability Evaluations.

Panax notoginseng (PN) has become the most widely used dietary supplement and herbal in Asian countries. The effect of micronization on PN is not entirely clear. The aim of this study was to investigate the effects of particle size of Panax notoginseng powder (PNP) and the potential to improve the bioavailability. The results showed that particle size reduction significantly changed the Panax notoginseng saponins (PNS) in vitro dissolution and in vivo pharmacokinetics. The size of the Panax notoginseng powder (PNP) ranges from 60 to 214 µm. The surface morphology and thermal properties of PNP were extensively characterized, and these changes in physicochemical properties of PNP provide a better understanding of the in vitro and in vivo release behaviors of PNS. The in vitro studies demonstrated that the dissolution of PNS and particle size were nonlinear (dose- and size-dependent). The pharmacokinetics parameters of PNP in rats were determined by UHPLC-MS/MS. Powder 4 (90.38 ± 8.28 µm) showed significantly higher AUC0-T values in plasma (P < 0.05). In addition, we also investigated the influence of the hydrothermal treatment of PNP. The results showed that the PNS in vitro release and in vivo bioavailability of PNP pretreatment at 40°C were the highest. This suggests that PNP with a particle size of around 90 µm and heat pretreatment at 40°C would be beneficial. These results provided an experimental basis, and it was beneficial to choose an appropriate particle size and hydrothermal temperature when PNP was used in clinical treatment.

Intersegmental plane simulation based on the bronchus-vein-artery triad in pulmonary segmentectomy.

BACKGROUND: Few reliable methods to simulate and evaluate the intersegmental plane have been reported. We introduce intersegmental plane simulation based on the bronchus-vein-artery triad in three-dimensionally reconstructed images from patients who underwent segmentectomy for early lung cancer. METHODS: We collected clinical data of consecutive patients with early-stage lung cancer who underwent three-dimensional imaging-guided single-port thoracoscopic segmentectomy at Department No. 1 of Thoracic Surgery at Fujian Medical University Fujian Union Hospital from January 2019 to July 2019. Patients were divided into two groups according to the application of intersegmental plane simulation and nodule analysis: the intersegmental plane group and the non-intersegmental plane group. General clinical characteristics, operation status, and postoperative recovery were compared between groups. The three-dimensional reconstruction results in the intersegmental plane group were analyzed and summarized. RESULTS: A total of 120 patients were included (61 in the intersegmental plane group and 59 in the non-intersegmental plane group). There were no significant differences between the two groups in general characteristics (all P>0.05). All target lesions were resected in both groups. There were no significant differences between groups in operation characteristics or postoperative recovery, with the exception of the duration of chest drainage and the rate of gross margin insufficiency. There were five cases of gross margin insufficiency in the non-intersegmental plane group. With three-dimensional imaging reconstruction, a total of 131 intersegmental veins could be used to evaluate the simulated intersegmental plane in 61 patients, with an average of 2.1±0.5 veins per patient. Two patients (3.3%) had one vein that could be used to evaluate the intersegmental plane, 50 patients (82.3%) had two, seven patients (11.3%) had three, and two patients (3.3%) had four. The total number of intersegmental veins located on the simulated intersegmental plane was 124 (94.7%), with an average of 2.0±0.6 veins per patient. The accuracy of intersegmental plane simulation was 91.8% (56/61). CONCLUSIONS: The bronchus-vein-artery triad in intersegmental plane simulation can assist surgeons in preoperative planning and can facilitate complete resection of early lung cancer with sufficient surgical margins.

Application of machine learning approaches to predict the 5-year survival status of patients with esophageal cancer.

BACKGROUND: Accurate prognostic estimation for esophageal cancer (EC) patients plays an important role in the process of clinical decision-making. The objective of this study was to develop an effective model to predict the 5-year survival status of EC patients using machine learning (ML) algorithms. METHODS: We retrieved the information of patients diagnosed with EC between 2010 and 2015 from the Surveillance, Epidemiology, and End Results (SEER) Program, including 24 features. A total of 8 ML models were applied to the selected dataset to classify the EC patients in terms of 5-year survival status, including 3 newly developed gradient boosting models (GBM), XGBoost, CatBoost, and LightGBM, 2 commonly used tree-based models, gradient boosting decision trees (GBDT) and random forest (RF), and 3 other ML models, artificial neural networks (ANN), naive Bayes (NB), and support vector machines (SVM). A 5-fold cross-validation was used in model performance measurement. RESULTS: After excluding records with missing data, the final study population comprised 10,588 patients. Feature selection was conducted based on the χ2 test, however, the experiment results showed that the complete dataset provided better prediction of outcomes than the dataset with removal of non-significant features. Among the 8 models, XGBoost had the best performance [area under the receiver operating characteristic (ROC) curve (AUC): 0.852 for XGBoost, 0.849 for CatBoost, 0.850 for LightGBM, 0.846 for GBDT, 0.838 for RF, 0.844 for ANN, 0.833 for NB, and 0.789 for SVM]. The accuracy and logistic loss of XGBoost were 0.875 and 0.301, respectively, which were also the best performances. In the XGBoost model, the SHapley Additive exPlanations (SHAP) value was calculated and the result indicated that the four features: reason no cancer-directed surgery, Surg Prim Site, age, and stage group had the greatest impact on predicting the outcomes. CONCLUSIONS: The XGBoost model and the complete dataset can be used to construct an accurate prognostic model for patients diagnosed with EC which may be applicable in clinical practice in the future.

A pathological complete response to neoadjuvant chemotherapy and immunotherapy in a non-small cell lung cancer patient.

Lung cancer is the leading cause of cancer-related mortality worldwide. Patients with locally advanced non-small cell lung cancer (NSCLC) have lower overall survival. Studies have shown that some patients with unresectable stage III NSCLC develop disease progression after initial chemoradiotherapy, and new treatment is needed to improve the prognosis of these patients. The rapid development of therapy has greatly changed and continued to renew the treatment strategy of advanced NSCLC. However, the clinical treatment for patients with the wild-type gene remains problematic, and chemotherapy with platinum are not yet considered satisfactory. Herein, we are reporting a case of a patient with wild-type gene mutation locally advanced NSCLC who was treated with neoadjuvant therapy by using combined targeted anti-PD-1 immunotherapy and chemotherapy. The percentage of tumor cells with membranous PD-L1 staining (tumor proportion score) was 90% or greater. After receiving all three cycles of treatment, the patient underwent video-assisted right upper lung lobectomy and wedge resection plus radical mediastinal lymph node dissection. Pathological section samples showed a pathological complete response. This experience has led us to believe that the subgroup of patients with unresectable advanced NSCLC may benefit from this strategy and may have an opportunity for radical surgery.

Integrative genomics analysis of various omics data and networks identify risk genes and variants vulnerable to childhood-onset asthma.

BACKGROUND: Childhood-onset asthma is highly affected by genetic components. In recent years, many genome-wide association studies (GWAS) have reported a large group of genetic variants and susceptible genes associated with asthma-related phenotypes including childhood-onset asthma. However, the regulatory mechanisms of these genetic variants for childhood-onset asthma susceptibility remain largely unknown. METHODS: In the current investigation, we conducted a two-stage designed Sherlock-based integrative genomics analysis to explore the cis- and/or trans-regulatory effects of genome-wide SNPs on gene expression as well as childhood-onset asthma risk through incorporating a large-scale GWAS data (N = 314,633) and two independent expression quantitative trait loci (eQTL) datasets (N = 1890). Furthermore, we applied various bioinformatics analyses, including MAGMA gene-based analysis, pathway enrichment analysis, drug/disease-based enrichment analysis, computer-based permutation analysis, PPI network analysis, gene co-expression analysis and differential gene expression analysis, to prioritize susceptible genes associated with childhood-onset asthma. RESULTS: Based on comprehensive genomics analyses, we found 31 genes with multiple eSNPs to be convincing candidates for childhood-onset asthma risk; such as, PSMB9 (cis-rs4148882 and cis-rs2071534) and TAP2 (cis-rs9267798, cis-rs4148882, cis-rs241456, and trans-10,447,456). These 31 genes were functionally interacted with each other in our PPI network analysis. Our pathway enrichment analysis showed that numerous KEGG pathways including antigen processing and presentation, type I diabetes mellitus, and asthma were significantly enriched to involve in childhood-onset asthma risk. The co-expression patterns among 31 genes were remarkably altered according to asthma status, and 25 of 31 genes (25/31 = 80.65%) showed significantly or suggestively differential expression between asthma group and control group. CONCLUSIONS: We provide strong evidence to highlight 31 candidate genes for childhood-onset asthma risk, and offer a new insight into the genetic pathogenesis of childhood-onset asthma.

Methylome Variation Predicts Exemestane Resistance in Advanced ER+ Breast Cancer.

BACKGROUND: More than 30% of estrogen receptor-positive breast cancers are resistant to primary hormone therapy, and about 40% that initially respond to hormone therapy eventually acquire resistance. Although the mechanisms of hormone therapy resistance remain unclear, aberrant DNA methylation has been implicated in oncogenesis and drug resistance. PURPOSE: We investigated the relationship between methylome variations in circulating tumor DNA and exemestane resistance, to track hormone therapy efficacy. METHODS: We prospectively recruited 16 patients who were receiving first-line therapy in our center. All patients received exemestane-based hormone therapy after enrollment. We collected blood samples at baseline, first follow-up (after 2 therapeutic cycles) and at detection of disease progression. Disease that progressed within 6 months under exemestane treatment was considered exemestane resistance but was considered relatively exemestane-sensitive otherwise. We obtained circulating tumor DNA-derived methylomes using the whole-genome bisulfide sequencing method. Methylation calling was done by BISMARK software; differentially methylated regions for exemestane resistance were calculated afterward. RESULTS: Median follow-up for the 16 patients was 19.0 months. We found 7 exemestane resistance-related differentially methylated regions, located in different chromosomes, with both significantly different methylation density and methylation ratio. Baseline methylation density and methylation ratio of chromosome 6 [32400000-32599999] were both high in exemestane resistance. High baseline methylation ratios of chromosome 3 [67800000-67999999] (P = .013), chromosome 3 [140200000-140399999] (P = .037), and chromosome 12 [101200000-101399999] (P = .026) could also predict exemestane resistance. During exemestane treatment, synchronized changes in methylation density and methylation ratio in chromosome 6 [32400000-32599999] could accurately stratify patients in terms of progression-free survival (P = .000033). Cutoff values of methylation density and methylation ratio for chromosome 6 [149600000-149799999] were 0.066 and 0.076, respectively. CONCLUSION: Methylation change in chromosome 6 [149600000-149799999] is an ideal predictor of exemestane resistance with great clinical potential.

Adjuvant chemoradiotherapy for patients with pathologic node-positive esophageal cancer following radical resection is associated with improved survival.

BACKGROUND: Depending on the pathological stage, patients with esophageal squamous cell carcinoma (ESCC) can experience poor prognosis after surgery. This study was designed to analyze the effect of various treatments on prognosis in pathologic node-positive esophageal cancer patients who undergo radical surgery. METHODS: We evaluated 210 pathologic stage IIb-IIIc patients (pT1-4aN + M0) who had undergone esophagectomy for thoracic ESCC from January 2013 to October 2015 at our institute. Surgery alone was applied in 65 patients, postoperative chemotherapy alone was applied in 112 patients, and postoperative adjuvant chemoradiotherapy was applied in 33 patients. Kaplan--Meier and Cox regression analysis were used to compare overall survival (OS) and disease-free survival (DFS). A nomogram was constructed to visualize the multivariate Cox regression analysis model. RESULTS: The median follow-up period was 49.4 months. The 3- and 5-year OS rates of the patients in the surgery group, postoperative chemotherapy group, postoperative chemoradiotherapy group were 55.4%, 61.6%, and 75.8%, and 30.1%, 44.0%, and 63.0% respectively. The 3- and 5-year DFS rates of the patients in the surgery group, postoperative chemotherapy group, postoperative chemoradiotherapy group were 44.6%, 52.7%, and 72.7%, and 20.0%, 24.1%, and 39.4%, respectively. Both the OS and DFS of the patients in the postoperative chemoradiotherapy group were better than those of the patients in the surgery and postoperative chemotherapy group. Among them, the OS of the postoperative radiotherapy group was longer than that of the surgery group (P=0.011) and the postoperative chemotherapy group (P=0.190), while the DFS of postoperative chemoradiotherapy group was longer than that of the surgery group and postoperative chemotherapy group, but the difference was not statistically significant (P>0.05). CONCLUSIONS: This study showed that postoperative adjuvant chemoradiotherapy could improve 3-year OS and DFS compared with treatment using surgery alone or postoperative chemotherapy alone. However, an evaluation of long-term prognosis requires a longer follow-up.

hsa_circRNA_100873 upregulation is associated with increased lymphatic metastasis of esophageal squamous cell carcinoma.

Circular RNAs (circRNAs) are a type of endogenous non-coding RNA with multiple binding sites that specifically bind to microRNAs (miRNAs) and serve an important role in cellular regulatory networks. Patients exhibit varying levels of lymphatic metastasis in a clinical setting. The present study investigated the association between circRNAs and lymphatic metastasis in esophageal squamous cell carcinoma (ESCC). The tissue samples were divided into three groups, including early tumor stage associated with advanced nodal stage (T1 group), advanced tumor stage associated with early nodal stage (T2 group) and healthy esophageal epithelial tissues as the control group (C group). Gene chip analysis identified circRNAs, and those with possible regulatory functions were validated by reverse transcription-quantitative polymerase chain reaction analysis (RT-qPCR). circRNAs containing miRNA response element (MRE) sequences were obtained, and circRNA/miRNA prediction software was used to predict miRNAs that may interact with circRNA. A total of 12,275 circRNAs were detected, including 861 with statistically significant differences. A comparison between the T1 and C groups identified 152 upregulated circRNAs and 431 downregulated ones, while a comparison between the T2 and C groups identified 187 upregulated and 481 downregulated circRNAs. A T1/T2 group comparison revealed that four circRNAs were upregulated and seven were downregulated (fold change >1.5; P<0.05). The RT-qPCR data and gene chip analysis consistently identified hsa_circRNA_100873 as differentially expressed among the examined groups. A total of five potential MREs and complementary sequences were selected for hsa_circRNA_100873. The results of the present study indicated that multiple differentially expressed circRNAs are involved in the pathogenesis of ESCC, and that upregulation of hsa_circRNA_100873 may be associated with increased lymphatic metastases in ESCC.

Management of the inter-segmental plane using the "Combined Dimensional Reduction Method" is safe and viable in uniport video-assisted thoracoscopic pulmonary segmentectomy.

BACKGROUND: The management of the intersegmental plane (ISP) is challenging during uniport video-assisted thoracoscopic (VATS) pulmonary segmentectomy. Staplers and electrocautery have been used extensively in ISP management. However, both of them have their respective drawbacks. Currently, we have provided a revised technique termed as "Combined Dimensional Reduction Method" (CDR method), for managing the ISP with combined application of ultrasonic scalpel and staplers. The study aimed to review the outcomes of patients who underwent uniport VATS segmentectomy with or without the CDR method in our institute and assess the feasibility and safety of the CDR method. METHODS: From March 2017 to February 2018, 220 patients who underwent uniport VATS segmentectomy were retrospectively reviewed. By using IQQA software, pulmonary structures were reconstructed as three-dimensional (3D) images, making the targeted structures could be identified preoperatively. For the management of the ISP, in the CDR group, we firstly used the ultrasonic scalpel to trim the 3D pulmonary structure along the intersegmental demarcation, making the remaining targeted parenchyma both sufficiently thin enough and located on a 2D plane; thus, enabling easy use of staplers in managing ISP. Whereas, in the non-CDR group, we only use the staplers to manage the ISPs. The clinical characteristics, complications, and postoperative pulmonary functions were compared between the two groups. RESULTS: Propensity score analysis generated 2 well-matched pairs of 71 patients in CDR and non-CDR groups. There was no 30-day postoperative death or readmission in either group. The CDR group was significantly associated with the shorter operative time (178.3±35.8 vs. 209.2±28.7 min) (P=0.031) and postoperative stay (4.5±2.3 vs. 5.7±4.2 days) (P=0.041), compared to the non-CDR group. Moreover, no significant difference was observed in blood loss, a period of chest tube drainage, a period of ultrafine tube drainage, and postoperative pulmonary complications between the two groups. Moreover, the recovery rate of postoperative forced expiratory volume in 1 second (FEV1) or vital capacity (VC) at 1 and 3 months after segmentectomy was comparable between them. CONCLUSIONS: The CDR method could make segmentectomy easier and more accurate, and therefore has the potential to be a viable and effective technique for uniport VATS pulmonary segmentectomy.