Expression of PTP4A1 in circulating tumor cells and its efficacy evaluation in patients with early- and intermediate-stage esophageal cancer.

The objective of this study is to investigate the expression of protein tyrosine phosphatase type I (PTP4A1) in circulating tumor cells (CTCs) in patients with early- and intermediate-stage esophageal cancer and its clinical value in evaluating patient prognosis. Tissue and peripheral blood samples were collected from patients with esophageal cancer, as well as their clinical data. Follow-up was performed on all patients. PTP4A1 expression in the CTCs of patients were analyzed by regression analysis, and its correlation with the clinical characteristics of esophageal cancer was discussed. The numbers of mixed tumor cells and T-CTCs were significantly correlated with lymph node metastasis. Advanced tumor-node metastasis (TNM) stage (odds ratio = 12.063) and lymph node metastasis (odds ratio = 13.541) were influencing factors of PTP4A1+MCTC expression disorders in patients with esophageal cancer. The receiver operating characteristic curve showed that TNM stage and lymph node metastasis had a high predictive efficiency for PTP4A1+MCTCs, with an area under the ROC curve of 0.725. PTP4A1+mixed tumor cells had strong predictive value for the efficacy of neoadjuvant therapy, with a sensitivity of 94.7% and a specificity of 63.6%. Advanced TNM stage and lymph node metastasis are influencing factors for increased CTCs and poor expression of PTP4A1 in patients with esophageal cancer.

Quantitative biochemical phenotypic heterogeneity of senescent macrophage at a single cell level by Synchrotron Radiation Fourier Transform Infrared Microspectroscopy.

Macrophage senescence plays an important role in pathophysiological process of age-related diseases such as atherosclerosis, chronic obstructive pulmonary disease (COPD), pulmonary fibrosis, and lung cancer. After macrophage senescence, the biochemical phenotypes related to biological functions showed great heterogeneity. However, the biochemical phenotype and phenotypic heterogeneity of senescent macrophage has not been fully understood. Exploring the phenotype of biochemical substances in senescent macrophage will be helpful for understanding the function of senescent macrophage and finding out the potential mechanism between immune macrophage senescence and age-related diseases. In this study, we employed SR-FTIR microspectroscopy to detect the biochemical phenotype and phenotypic heterogeneity of single macrophage. The whole infrared spectra of senescent macrophages shifted, indicating biochemical substance changes within senescent macrophages. PCA and intercellular Euclidean distance statistical analysis based on specific spectra regions revealed dynamic changes of lipids and proteins during macrophage senescence. This proved that SR-FTIR microspectroscopy is an effective tool to detect the single cell biochemical phenotype transformation and phenotypic heterogeneity during macrophage senescence. It is of great significance to provide an evaluation method or clue for the study of cellular functions related to intracellular biochemical substances.

Long noncoding RNA LIPH-4 promotes esophageal squamous cell carcinoma progression by regulating the miR-216b/IGF2BP2 axis.

INTRODUCTION: Esophageal squamous cell carcinoma (ESCC) represents a major malignancy with poor clinical outcomes. Long noncoding RNAs (lncRNAs) are known to regulate the development and progression of multiple cancers. However, how lncRNAs are involved in ESCC is currently undefined. METHODS: LIPH-4 levels in ESCC tissue specimens and cells were assessed by qRT-PCR. The biological function of LIPH-4 was examined in cell and animal studies, applying CCK-8, EdU, colony formation and flow cytometry assays as well as xenograft model experiments. The underlying mechanisms of action of LIPH-4 were explored through bioinformatics, luciferase reporter assay, RNA-immunoprecipitation assay and immunoblot. RESULTS: We identified a novel lncRNA, LIPH-4, which showed elevated amounts in ESCC tissues and positive correlations with increased tumor size and poor prognosis in ESCC patients. Functional studies showed that LIPH-4 promoted the growth, mediated cell cycle progression and inhibited apoptosis in ESCC cells in vitro, and promoted tumor growth in mice. In terms of mechanism, LIPH-4 could bind to miR-216b and act as a competing endogenous RNA (ceRNA) to induce the expression of miR-216's target gene IGF2BP2. LIPH-4 played an oncogenic role in ESCC through the miR-216b/IGF2BP2 axis. CONCLUSIONS: This study suggested that LIPH-4 functions as a novel oncogenic lncRNA by acting as a ceRNA for miR-216b to regulate IGF2BP2, indicating LIPH-4 likely constitutes a prognostic biomarker and therapeutic target in ESCC.

Oncogenic roles of the lncRNA LINC00460 in human cancers.

Long noncoding RNAs (lncRNAs) represent an important group of endogenous RNAs with limit protein-encoding capability, with a length of more than 200 nucleotides. Emerging evidence have demonstrated that lncRNAs are greatly involved in multiple cancers by playing critical roles in tumor initiation and progression. Long intergenic non-protein coding RNA 460 (LINC00460), a novel cancer-related lncRNA, exhibits abnormal expression and oncogenic function in multiple cancers, and positively correlates with poor clinical characteristics of cancer patients. LINC00460 has also been shown to be a promising biomarker for diagnosis as well as prognostic evaluation in cancer patients. In this review, we briefly summarized recent knowledge on the expression, functional roles, molecular mechanisms, and diagnostic and prognostic values of LINC00460 in human malignancies.

Perioperative Outcomes of Video-Assisted Thoracoscopic Surgery Versus Open Thoracotomy After Neoadjuvant Chemoimmunotherapy in Resectable NSCLC.

Background: Neoadjuvant chemoimmunotherapy becomes more widespread in the treatment of NSCLC, but few studies have reported the details of surgical techniques and perioperative challenges following neoadjuvant chemoimmunotherapy until now. The primary aim of our study was to address the feasibility and safety of pulmonary resection after neoadjuvant chemoimmunotherapy via different surgical approaches, video-assisted thoracoscopic surgery (VATS) and open thoracotomy. Methods: Patients with an initial diagnosis of clinical stage IB-IIIB(T3-4N2) NSCLC, who received neoadjuvant chemoimmunotherapy and surgery between January 2019 and August 2021 were included. Patients were retrospectively divided into two groups (VATS, and thoracotomy), and differences in perioperative, oncological, and survival outcomes were compared. Results: In total, there were 131 NSCLC patients included. Surgery was delayed beyond 42 days in 21 patients (16.0%), and radical resection (R0) was achieved in 125 cases (95.4%). Lobectomy was the principal method of pulmonary resection (102 cases, 77.9%) and pneumonectomy was performed in 11 cases (8.4%). Postoperative complications within 30 days occurred in 28 patients (21.4%), and no 90-day mortality was recorded. There were 53 patients (38.5%) treated with VATS, and 78 (59.5%) with open thoracotomy. VATS could achieve similar definitive resection rates, postoperative recovery courses, comparable morbidities, and equivalent RFS rates(p>0.05), with the advantages of reduced operative time (160.1 ± 40.4 vs 177.7 ± 57.7 min, p=0.042), less intraoperative blood loss (149.8 ± 57.9 vs 321.2 ± 72.3 ml, p=0.021), and fewer intensive care unit(ICU) stays after surgery (3.8% vs 20.5%, p=0.006) compared with open thoracotomy. However, the mean number of total lymph nodes resected was lower in the VATS group (19.5 ± 7.9 vs 23.0 ± 8.1, p=0.013). More patients in the thoracotomy group received bronchial sleeve resection/bronchoplasty (53.8% vs 32.1%, p=0.014) and vascular sleeve resection/angioplasty (23.1% vs 3.8%, p=0.003). After propensity score matching (PSM) analysis, VATS still had the advantage of fewer ICU stays after surgery (2.3% vs. 20.5%, p=0.007). Conclusions: Our results have confirmed that pulmonary resection following neoadjuvant PD-1 inhibitors plus chemotherapy is safe and feasible. VATS could achieve similar safety, definitive surgical resection, postoperative recovery, and equivalent oncological efficacy as open thoracotomy, with the advantage of fewer ICU stays after surgery.

Identification and validation of HOXD3 and UNC5C as molecular signatures in keloid based on weighted gene co-expression network analysis.

BACKGROUND: Keloid is a benign proliferative disease characterized by excessive deposition of extracellular matrix collagen during skin wound healing. The mechanisms of keloid formation have not been fully elucidated, and the current treatment methods are not effective for all keloid patients. Therefore, there is an urgent need to find more effective therapies, and our research focused on identifying characteristic molecular signatures of keloid to explore potential therapeutic targets. METHODS: Gene expression profiles of keloid and control group samples were retrieved from the GEO database. Taking the GSE113619 dataset as the training set, the dataset collected skin tissues from non-lesion sites of healthy and keloid-prone individuals, denoted as Day0. The second sampling was performed 42 days later at the original sampling site of control and keloid groups, denoted as Day42.The 'limma' package and Venn diagram identified differentially expressed genes (DEGs) specific to keloid day42 versus day0 samples. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Reactome pathway functional enrichment, and annotation of the characteristic genes were conducted on the Metascape website. Ingenuity canonical pathways, disease & function enrichment analysis and gene interaction network were performed and predicted in Ingenuity Pathway Analysis (IPA) software. Key module genes related to keloid were filtered out by Weighted Gene Co-expression Network Analysis (WGCNA). We utilized the Least Absolute Shrinkage and Selection Operator (LASSO) algorithm to screen the characteristic genes in keloid by the 'glmnet' package. The area under the curve (AUC) of receiver operating characteristic (ROC) was utilized to determine the effectiveness of potential signatures in discriminating keloid samples from normal samples and performed by using the 'pROC' package. The enrich scores of 24 immune cells in each sample were calculated by the single-sample gene set enrichment analysis (ssGSEA) algorithm， and then the Gene Set Variation Analysis (GSVA) was performed. Finally, RNA from 4 normal and 6 keloid samples was extracted, and RT-qPCR and Western Blot validated the expression of characteristic genes. RESULTS: A total of 640 DEGs specific to keloid day42 versus day0 samples were detected. 69 key module genes were uncovered and implicated in 'NCAM signaling for neurite out-growth', 'oncogenic MAPK signaling', 'transmission across chemical synapses' pathways, and the mitotic cell cycle-related processes. Five characteristic genes (MTUS1, UNC5C, CEP57, NAA35, and HOXD3) of keloid were identified by LASSO, and among which UNC5C and HOXD3 were validated by ROC plot in external dataset, RT-qPCR and Western Blot in validation samples. The result of ssGSEA indicated that the infiltration of neutrophils showed a relatively higher abundance and natural killer cells with relatively low enrichment in the keloid group compared to the control group. UNC5C was correlated with more immune cells compared with other characteristic genes. CONCLUSION: In this study, characteristic genes associated with keloid were identified by bioinformatic approaches and verified in clinical validation samples, providing potential targets for the diagnosis and treatment of keloid.

LncRNA GACAT3 promotes esophageal squamous cell carcinoma progression through regulation of miR-149/FOXM1.

BACKGROUND: The long noncoding RNA gastric cancer associated transcript 3 (GACAT3) has been demonstrated to be implicated in the carcinogenesis and progression of many malignancies. However, GACAT3's levels and role in esophageal squamous cell carcinoma (ESCC) has not been elucidated. METHODS: GACAT3 amounts were investigated in ESCC tissues and cell lines by qPCR. Its biological functions were examined by CCK-8 assay, colony formation assay, flow cytometry, wound healing assay, transwell assay, and xenograft model establishment. The relationship between GACAT3 and miR-149 was assessed by dual-luciferase reporter assay. RESULTS: GACAT3 amounts were elevated in ESCC tissue and cell specimens. Functional studies showed that GACAT3 silencing reduced the proliferation, migration and invasion of cultured ESCC cells, and decreased tumor growth in mice. Furthermore, GACAT could directly interact with miR-149. In addition, colony formation and invasion assays verified that GACAT3 promotes ESCC tumor progression through miR-149. Moreover, GACAT3 acted as a competing endogenous RNA (ceRNA) to modulate FOXM1 expression. CONCLUSIONS: These findings indicate that GACAT3 functions as an oncogene by acting as a ceRNA for miR-149 to modulate FOXM1 expression in ESCC, suggesting that GACAT3 might constitute a therapeutic target in ESCC.

miR-21-5p/SMAD7 axis promotes the progress of lung cancer.

BACKGROUND: Lung cancer is one of the most common malignant tumors threatening human health. The aim of this study was to investigate the function of miR-21-5p in lung cancer progression. METHODS: We analyzed the expression levels of miR-21-5p in lung cancer tissues and cell lines. The qRT-PCR and MTT assays were performed after transfection with miR-21-5p mimic, inhibitor and negative control into lung cancer cells. RESULTS: Luciferase reporter assays showed miR-21-5p directly target SMAD7. The miR-21-5p inhibitor significantly suppressed lung cancer cell proliferation, invasion and migration. We found that SMAD7 was upregulated in lung cancer tissue. In addition, we found that SMAD7 inhibited lung cancer cell proliferation and miR-21-5p mimic damaged the inhibitory effect of SMAD7. CONCLUSIONS: miRNA-21-5p may promote cell proliferation, migration and invasion by spoiling SMAD7 expression in lung cancer cells.

LncRNA SNHG16 as a potential biomarker and therapeutic target in human cancers.

Long non-coding RNAs (lncRNAs) represent an important class of RNAs comprising more than 200 nucleotides, which are produced by RNA polymerase II. Although lacking an open reading framework and protein-encoding activity, lncRNAs can mediate endogenous gene expression by serving as chromatin remodeler, transcriptional or post-transcriptional modulator, and splicing regulator during gene modification. In recent years, increasing evidence shows the significance of lncRNAs in many malignancies, with vital roles in tumorigenesis and cancer progression. Moreover, lncRNAs were also considered potential diagnostic and prognostic markers in cancer. The lncRNA small nuclear RNA host gene 16 (SNHG16), found on chromosome 17q25.1, represents a novel tumor-associated lncRNA. SNHG16 was recently found to exhibit dysregulated expression in a variety of malignancies. There are growing evidence of SNHG16's involvement in characteristics of cancer, including proliferation, apoptosis, together with its involvement in chemoresistance. In addition, SNHG16 has been described as a promising diagnostic and prognostic biomarker in cancer patients. The current review briefly summarizes recently reported findings about SNHG16 and discuss its expression, roles, mechanisms, and diagnostic and prognostic values in human cancers.

Parthenolide Inhibits Angiogenesis in Esophageal Squamous Cell Carcinoma Through Suppression of VEGF.

BACKGROUND: Parthenolide (PT), the effective active ingredient of the medicinal plant, feverfew (Tanacetum parthenium), has been used as an anti-inflammatory drug due to its involvement in the inhibition of the NF-кB pathway. Moreover, recent studies have demonstrated the anti-tumor effect of PT in several cancers. However, the effect of PT on esophageal carcinoma remains unclear to date. In this study, we examined the inhibitory effects of PT and its underlying mechanism of action in human esophageal squamous cell carcinoma (ESCC) cells - Eca109 and KYSE-510. METHODS: The proliferation ability of Eca109 and KYSE-510 treated with PT was detected using the Cell Counting Kit-8 and colony forming assay. The Transwell assay and the wound healing assay were used to analyze the cell invasion and migration ability, respectively. The tube formation assay was used to investigate the effect of PT on tube formation of endothelial cells. The expression level of NF-кB, AP-1 and VEGF was analyzed by Western blot. RESULTS: We demonstrated that PT attenuates the proliferation and migration ability of ESCC cells in vitro and also inhibits tumor growth in the mouse xenograft model. In addition, PT exhibited anti-angiogenesis activity by weakening the proliferation, invasion and tube formation of endothelial cells in vitro and reduced microvessel density in the xenograft tumors. Further studies revealed that PT reduced the expression level of NF-кB, AP-1 and VEGF in ESCC cells. CONCLUSION: Collectively, the results of our study demonstrated that PT exerts anti-tumor and anti-angiogenesis effects possibly by inhibiting the NF-кB/AP-1/VEGF signaling pathway on esophageal carcinoma and might serve as a promising therapeutic agent for ESCC.

Author Correction: Genome-wide analyses of long non-coding RNA expression profiles and functional network analysis in esophageal squamous cell carcinoma.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

SNHG7: A novel vital oncogenic lncRNA in human cancers.

Long noncoding RNAs (lncRNAs) are a group of RNAs that lack protein-coding ability, with lengths greater than 200 nucleotides. Increasing evidence has indicated that they mediate multiple physiological and pathological processes by regulating gene expression at the epigenetic, transcriptional, post-transcriptional, and translational levels. The deregulation of lncRNAs was demonstrated to have tumor suppressive or oncogenic effects, and thus, these molecules play vital regulatory roles in tumor initiation and progression. Small nucleolar RNA hostgene 7 (SNHG7) is a lncRNA located on chromosome 9q34.3. Different studies have explored the potential role of SNHG7 in the development and progression of multiple human malignancies such as bladder, breast, colorectal, esophageal, gastric, and prostate cancer, as well as osteosarcoma, among others, and high expression predicts poor prognosis and poor survival for such patients. Moreover, this molecule can promote proliferation and metastasis, while inhibiting apoptosis in cancer cells. The present review highlights the latest insights into the expression, functional roles, and molecular mechanisms of SNHG7 in different human malignancies.

Long noncoding RNA lnc-ABCA12-3 promotes cell migration, invasion, and proliferation by regulating fibronectin 1 in esophageal squamous cell carcinoma.

Long noncoding RNAs (lncRNAs) have been shown to play important roles in human cancers, including esophageal squamous cell carcinoma (ESCC). We previously demonstrated that a novel lncRNA, lnc-ABCA12-3, was overexpressed in ESCC tissues. However, the exact function of lnc-ABCA12-3 is unknown. In the current study, we aimed to evaluate the expression of lnc-ABCA12-3 in ESCC and to explore the potential mechanism of lnc-ABCA12-3 in cell migration, invasion, and proliferation. We showed that lnc-ABCA12-3 was upregulated in ESCC tumor tissues and cell lines. The increased expression of lnc-ABCA12-3 was positively associated with advanced tumor-node-metastasis stages and poor prognosis. The knockdown of lnc-ABCA12-3 inhibited the cell migration, invasion, and proliferation abilities of KYSE-510 and Eca-109 cells. We also found that fibronectin 1 (FN1) was upregulated in ESCC tumor tissues. The expression of FN1 messenger RNA was positively correlated with the expression of lnc-ABCA12-3 in ESCC tumor tissues. After lnc-ABCA12-3 knockdown, the expression of FN1 was downregulated. In addition, the overexpression of FN1 restored the abilities of cell migration, invasion and proliferation in Eca-109 cells. Further studies indicated that lnc-ABCA12-3 acted as a competing endogenous RNA for miR-200b-3p to regulate FN1 expression. In conclusion, these results suggest that lnc-ABCA12-3 is a novel oncogene in tumorigenesis and that its high expression is related to a poor prognosis for patients with ESCC. lnc-ABCA12-3 promotes cell migration, invasion, and proliferation via the regulation of FN1 in ESCC. Our data suggest that lnc-ABCA12-3 might serve as a potential prognostic biomarker and therapeutic target for ESCC.

Involvement of noncoding RNAs in epigenetic modifications of esophageal cancer.

Esophageal cancer (EC) is a serious digestive malignancy and is a leading cause of cancer-related mortality. Apart from genetic mutations, many epigenetic alterations including DNA methylation and histone modifications associated with chromatin remodeling have been identified in the regulation of gene expression in EC. Recently, noncoding RNAs, and mainly lncRNAs and miRNAs, have been revealed to be involved in the epigenetic regulation of EC. In this review, we focus on describing new insights on epigenetic processes associated with noncoding RNAs, which have been characterized to be responsible for the development and progression of EC.

Genome-wide analyses of long non-coding RNA expression profiles and functional network analysis in esophageal squamous cell carcinoma.

Esophageal cancer (EC) is a serious malignancy and that is the fifth leading cause of cancer-related death worldwide. Esophageal squamous cell carcinoma (ESCC) is the main subtype of EC in China. In recent years, long non-coding RNAs (lncRNAs) have demonstrated to be novel tumor-associated regulatory factors. However, the functions and mechanisms of lncRNAs in ESCC have not been fully understood. In this study, we attempted to construct Genome-wide expression profiles of lncRNAs and their potential functions in ESCC. By using microarray, we found a total of 2,366 lncRNAs (1,032 upregulated and 1,334 downregulated) and 3,052 mRNAs (1,477 upregulated and 1,575 downregulated) were differentially expressed between the paired five ESCC tumor tissues and adjacent normal esophageal tissues (fold change, FC ≥2.0 or ≤0.5, p ≤ 0.05). Eight lncRNAs were detected by qRT-PCR to verify the results of the microarray, and the clinicopathological parameters were analyzed in 53 patients with ESCC. GO analysis and KEGG pathway analysis showed that the main biological functions of these abnormal lncRNAs were related to immune response, extracellular vesicular exosome, and protein binding. At the same time, the cis and trans models were used to analyze the potential synergistic regulatory relationship between lncRNAs and their potential target genes. Related genes were the processes that affect cell growth, differentiation, and migration. Then we mapped the lncRNAs-mRNAs co-expression pattern by calculating the PCCs of each lncRNA and mRNA expression value. Furthermore, we investigated the function and potential mechanism of a novel highly expressed lncRNA, lnc-KIAA1244-2, and found that its expression is associated with tumor size, N classification and clinical stage. Knockdown of lnc-KIAA1244-2 inhibited the cell proliferation and inhibited the TNFAIP3 expression in Eca-109 cells. Taken together, the expression patterns of lncRNAs and mRNAs in ESCC tumor tissues are different from those in normal adjacent tissues, and some abnormal expressed lncRNAs may play important roles in the development and progression of ESCC. Lnc-KIAA1244-2 could promote the cell proliferation of ESCC cells and might be a potent therapeutic target for ESCC.

Primary small cell carcinoma of the esophagus: Comparison between a Chinese cohort and Surveillance, Epidemiology, and End Results (SEER) data.

BACKGROUND: The optimal standard treatment for primary small cell carcinoma of the esophagus (SCCE) remains undetermined. In this study, we conducted two areas of research on SCCE. First, we analyzed differences in SCCE characteristics between Chinese and U.S. PATIENTS: Second, we evaluated optimal treatment strategies for SCCE in the Chinese cohort. METHODS: Data from 137 Chinese SCCE patients collected from two cancer centers in China were compared with 385 SCCE patients registered in the U.S. SEER program. Prognostic factors were further analyzed in the Chinese group. Propensity score matching (PSM) was used to balance baseline features between the groups. RESULTS: There were more Chinese SCCE patients with regional stage disease (41.6%) and surgery was the principal local therapy (78.1%), while 51.7% of U.S. patients was at advanced stages and tended to receive radiotherapy as the main therapy (45.2%). Median overall survival (MST) of Chinese patients was 15.0 months, compared with 8.0 months for U.S. patients (P < 0.001). However, the survival differences between groups disappeared after PSM (MST: 12.5 m vs 9.0 m, P = 0.144). Further analysis found that surgery tended to achieve clinical benefits only for patients with localized disease (T1-4aN0M0). Radiotherapy and chemotherapy may prolong survival in patients with regional and extensive disease. CONCLUSIONS: Although there are huge differences in the tumor characteristics and treatment modalities of SCCE between Chinese and U.S. patients, the prognosis of SCCE is equally poor in both. Surgery should be considered for patients with localized disease, while chemoradiotherapy is recommended for patients with regional and extensive disease.

Role of lncRNA and EZH2 Interaction/Regulatory Network in Lung Cancer.

Lung cancer is the leading cause of cancer-related deaths worldwide. Long non-coding RNAs (lncRNAs) are non-protein-coding transcripts and longer than 200 nucleotides. LncRNAs have been demonstrated to modulate gene expression at transcriptional, post-transcriptional, as well as epigenetic levels in lung cancer. Interestingly, compelling studies have revealed that lncRNAs participated in the EZH2 oncogenic regulatory network. EZH2 plays an important role in the initiation, progression and metastasis of cancer. On one hand, lncRNAs can directly bind to EZH2, recruit EZH2 to the promoter region of genes and repress their expression. On the other hand, lncRNAs can also serve as EZH2 effectors or regulators. In this review, we summarized the types of lncRNA-EZH2 interaction and regulatory network identified till date and discussed their influence on lung cancer. Better understanding regarding the interaction and regulatory network will provide new insights on lncRNA- or EZH2-based therapeutic development in lung cancer.

Efficacy comparison of transcervical video-assisted mediastinoscopic lymphadenectomy combined with left transthoracic esophagectomy versus right transthoracic esophagectomy for esophageal cancer treatment.

BACKGROUND: This study aimed to propose a new surgical strategy, i.e., the transcervical video-assisted mediastinoscopic lymphadenectomy (VAMLA) with esophagectomy via the left transthoracic approach for patients with esophageal cancer (EC), and to compare the outcomes with those of esophagectomy via the right thoracic approach. METHODS: From December 2014 to March 2016, 49 cases were enrolled in this non-randomized concurrent control study. Twenty-eight patients with EC who underwent transcervical VAMLA with esophagectomy via the left transthoracic approach were assigned into the study group, while 21 EC patients undergoing esophagectomy via the right transthoracic approach during the same period were enrolled into the control group. Operative outcomes including operative time, the numbers of removed lymph nodes, intraoperative blood loss, the length of hospital stay, and postoperative complications in both groups were evaluated and compared. RESULTS: There were no significant differences in the baseline profiles between the two groups, and all patients in the two groups successfully underwent the surgery. There was a significant difference between transcervical VAMLA with esophagectomy via the left thoracic approach and esophagectomy via the right thoracic approach with regard to the number of all dissected lymph nodes [(29.0 ± 8.7) vs. (17.8 ± 8.1), p < 0.05], dissected superior mediastinal lymph nodes [(11.2 ± 5.0) vs. (3.7 ± 2.9), p < 0.05], and dissected in the recurrent laryngeal nerve lymph nodes [(5.6 ± 3.5) vs. (2.3 ± 2.1), p < 0.05]. No significant differences were observed in the operative time, intraoperative blood loss, length of postoperative hospital stay, number of dissected abdominal lymph nodes, postoperative pulmonary complications (pneumonia and atelectasis), anastomotic fistula, chylothorax, and vocal cord paralysis (p > 0.05). CONCLUSION: Transcervical VAMLA combined with esophagectomy via the left thoracic approach appears technically feasible and safe and shows advantages in the number of dissected superior mediastinal lymph nodes, suggesting that it may serve as a new treatment option for patients with esophageal carcinoma.

Minimally invasive esophagectomy via Sweet approach in combination with cervical mediastinoscopy for esophageal squamous cell carcinoma: a case series.

OBJECTIVE: Minimally invasive esophagectomy (MIE) is increasingly used for the treatment of esophageal cancer. However, MIE via the Sweet approach has seldom been reported owing to the challenging procedure for a mediastinal lymph node. Thus, the approach of MIE via left-sided thoracoscopy coupled with video-assisted cervical mediastinoscopy (MIE-SM) was explored for eradicating the mediastinal lymph nodes and recurrent laryngeal nerve; the incidence of perioperative complications, mortality, and surgical radicality were analyzed. MATERIALS AND METHODS: Thirty patients with esophageal carcinoma underwent MIE-SM between June 2014 and February 2016. The primary outcome was postoperative morbidity within 2 weeks postsurgery. The secondary outcome was surgical radicality, including the circumferential margins, and the number of lymph nodes dissected. RESULTS: The MIE-SM was completed in all patients within 367.6±68.7 minutes. The incidences of postoperative morbidities including pulmonary complications, anastomotic leakage, chylothorax, or recurrent nerve injury were 43.3%. CONCLUSION: The MIE-SM was utilized for the first time to reduce the disadvantage of purely Sweet and McKeown approach, with favorable efficacy in the mediastinal and laryngeal recurrent nerve lymph node eradication. Thus, MIE-SM might be a promising alternative approach in treating esophageal cancer in selected patients.

Prostaglandin E2 inhibits collagen synthesis in dermal fibroblasts and prevents hypertrophic scar formation in vivo.

Hypertrophic scarring is a common dermal fibroproliferative disorder characterized by excessive collagen deposition. Prostaglandin E2 (PGE2 ), an important inflammatory product synthesized via the arachidonic acid cascade, has been shown to act as a fibroblast modulator and to possess antifibroblastic activity. However, the mechanism underlying the antifibrotic effect of PGE2 remains unclear. In this study, we explored the effects of PGE2 on TGF-ß1-treated dermal fibroblasts in terms of collagen production and to determine the regulatory pathways involved, as well as understand the antiscarring function of PGE2 in vivo. We found that PGE2 inhibited TGF-ß1-induced collagen synthesis by regulating the balance of matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinase (TIMP). It did so by upregulating cAMP through the E prostanoid (EP)2 receptor. We determined that inhibition of the TGF-ß1/Smad pathway by PGE2 is associated with its ability to inhibit collagen synthesis. An in vivo study further confirmed that PGE2 inhibits hypertrophic scar formation by decreasing collagen production. Our results demonstrate that the novel anti-scarring function of PGE2 is achieved by balancing MMPs/TIMP expression and decreasing collagen production.