Minimally invasive esophagectomy with non-invasive ventilation by laryngeal mask-assisted anesthesia for esophageal squamous cell carcinoma: case report.

Minimally invasive esophagectomy for cancer surgery remains associated with significant morbidity and surgical complications across the globe. Non-intubation video-assisted thoracic surgery (NIVATS) has been successfully employed in lung resection in recent years, but there are few reported cases with regard to the safety and feasibility of this approach in radical esophagectomy for patients with esophageal cancers. We present 4 consecutive cases with esophageal squamous cell carcinoma (ESCC) who received minimally invasive McKeown's esophagectomy under non-intubation general anesthesia from November 2022 to April 2023. All these patients were aged from 55 to 75 years old and were pathologically diagnosed with ESCC. All procedures of McKeown's esophagectomy in these patients were completed with non-invasive ventilation by laryngeal mask-assisted anesthesia. Operation duration ranged from 185 to 395 minutes and the estimated blood loss ranged from 25 to 60 ml in these 4 cases. No severe hypoxia was observed and transient hypercapnia was resolved intraoperatively. None of them was converted to endotracheal intubation with mechanical ventilation or to thoracotomy. The number of retrieved lymph nodes in mediastinum were 21-27 and all patients received R0 surgery with pathological stage as T1bN0M0 to T3N2M0. There was no serious complication (Clavien-Dindo grade III-IV) observed perioperatively and they were all discharged 11-14 days after the surgery with resumption of oral feeding. They are all alive without tumor recurrence at the date of data collection. The safety and efficacy of minimally invasive esophagectomy with non-invasive ventilation by laryngeal mask-assisted anesthesia for patients with ESCC are warranted for explored in a larger cohort study.

Circular RNA circCHSY1 silencing inhibits the malignant progression of esophageal squamous cell carcinoma.

BACKGROUND: CircRNAs play a crucial role in the regulation of various cancers. This study aims to investigate the involvement of circCHSY1 in the development of esophageal squamous cell carcinoma (ESCC). METHODS: RNA levels were quantified using qRT-PCR, and protein levels were measured by western blot. The stability of circCHSY1 was analyzed using RNase R. The functional effect of circCHSY1 on cell behavior was evaluated by CCK-8, EdU, flow cytometry, transwell, tube formation, and xenograft tumor model assays. The associations among circCHSY1, miR-1229-3p, and Tectonic-1 (TCTN1) were certified by bioinformatics analysis, dual-luciferase reporter assay, and RNA pull-down assay. RESULTS: CircCHSY1 was up-regulated in both ESCC tissues and cell lines in comparison with the control groups. Knockdown of circCHSY1 inhibited the proliferation, migration, invasion, and tube formation and promoted apoptosis of ESCC cells. Mechanistically, circCHSY1 targeted miR-1229-3p, which was downregulated in ESCC tissues and cells. Inhibition of miR-1229-3p attenuated the effects mediated by circCHSY1 suppression. Besides, miR-1229-3p bound to TCTN1, and TCTN1 overexpression restored miR-1229-3p-induced effects in ESCC cells. Animal experiments revealed that circCHSY1 silencing suppressed tumor tumorigenesis in vivo. CONCLUSION: CircCHSY1 contributed to ESCC cell malignancy, and the underlying mechanism involved the circCHSY1/miR-1229-3p/TCTN1 axis, providing potential therapeutic targets for ESCC.

Triptolide inhibits esophageal squamous cell carcinoma progression by regulating the circNOX4/miR-153-3p/SATB1 signaling pathway.

BACKGROUND: To explore the role and mechanism of triptolide in regulating esophageal squamous cell carcinoma (ESCC) progression by mediating the circular RNA (circRNA)-related pathway. METHODS: The expression levels of circNOX4, miR-153-3p and special AT-rich sequence binding protein-1 (SATB1) were measured by qRT-PCR. Cell proliferation was confirmed by cell counting kit-8 assay and colony formation assay. Flow cytometry was employed to measure cell apoptosis and cell cycle process. Moreover, cell migration and invasion were detected using transwell assay. The protein levels of epithelial-mesenchymal transformation markers and SATB1 were determined by western blot analysis. Furthermore, dual-luciferase reporter assay and RIP assay were performed to confirm the interaction between miR-153-3p and circNOX4 or SATB1. Xenograft tumor models were built to verify the effects of triptolide and circNOX4 on ESCC tumor growth. RESULTS: CircNOX4 was highly expressed in ESCC tissues and cells, and its expression could be reduced by triptolide. Triptolide could inhibit ESCC proliferation, cell cycle process, migration, invasion, EMT process, and promote apoptosis, while these effects were reversed by circNOX4 overexpression. MiR-153-3p could be sponged by circNOX4, and the promotion effect of circNOX4 on the progression of triptolide-treated ESCC cells was abolished by miR-153-3p overexpression. SATB1 was a target of miR-153-3p. Also, SATB1 knockdown reversed the enhancing effect of miR-153-3p inhibitor on the progression of triptolide-treated ESCC cells. Triptolide reduced ESCC tumor growth by regulating the circNOX4/miR-153-3p/SATB1 axis. CONCLUSION: Triptolide could hinder ESCC progression, which was mainly achieved by regulating the circNOX4/miR-153-3p/SATB1 axis.

Occipital artery-posterior inferior cerebellar artery bypass: a cadaveric feasibility study.

PURPOSE: To demonstrate that occipital artery (OA)-p1 posterior inferior cerebellar artery (PICA) bypass can be an alternative for complex posterior circulation aneurysms. METHODS: A far-lateral approach to craniotomy was performed on 20 cadaveric specimens, and the OA was obtained 'in-line.' Its length, diameter, and the number of p1/p2 and p3 segmental perforators were determined, and the relationship between the caudal loop and cerebellar tonsil position was also assessed. The distance between the PICA's origin and the cranial nerve XI (CN XI), the buffer length above the CN XI after dissection, the OA length required to complete the OA-p1/p3 PICA bypass, and the p1 and p3 segment diameters were all measured. A bypass training practical scale (TSIO) was used to evaluate the quality of the anastomosis. RESULTS: All specimens underwent OA-p1 PICA end-to-end bypass and had favorable results for the TSIO score, 15 sides underwent OA-p3 PICA end-to-side bypass, and the other bypass protocols were less common. The buffer length above the CN XI after dissection, the distance between the PICA's origin and the CN XI, and the first perforator were all of sufficient length. The direct length of the OA needed to complete the OA-p1 PICA end-to-end bypass was significantly less than the available length and the OA-p3 PICA end-to-side bypass, with the OA matching the p1 segment diameter. The number of p1 perforators was less than that of p3, and the OA diameter was equal to that of the p1 segment. CONCLUSION: OA-p1 PICA end-to-end bypass is a feasible alternative in cases in which p3 segment has high caudal loops or anatomic anomalies.

Perioperative outcomes of neoadjuvant immunotherapy plus chemotherapy and neoadjuvant chemoradiotherapy in the treatment of locally advanced esophageal squamous cell carcinoma: a retrospective comparative cohort study.

Background: Neoadjuvant chemoradiotherapy (nCRT) is recommended as the preferred treatment for locally advanced esophageal squamous cell carcinoma. Recent studies have shown that immune checkpoint inhibitors are beneficial in treating advanced esophageal cancer. Therefore, a growing number of clinical centers are conducting trials of neoadjuvant immunotherapy or neoadjuvant immunotherapy plus chemotherapy (nICT) in patients with locally advanced resectable esophageal cancer. Immunocheckpoint inhibitors are expected to play a role in neoadjuvant therapy for esophageal cancer. However, there were few studies comparing nICT with nCRT. This study compared the efficacy and safety of nICT with that of nCRT administered prior to esophagectomy in patients with resectable locally advanced esophageal squamous cell carcinoma (ESCC). Methods: The study included patients with locally advanced resectable ESCC who were scheduled to receive neoadjuvant therapy at Gaozhou People's Hospital from January 1, 2019, to September 1, 2022. The enrolled patients were divided into 2 groups (nCRT or nICT) according to their neoadjuvant therapy regimen. The 2 groups were compared for their baseline data, the incidence of adverse events during neoadjuvant therapy, the clinical evaluation after neoadjuvant therapy, perioperative indicators, and the incidence of postoperative complications and postoperative pathological remission. Results: A total of 44 patients were enrolled; 23 in the nCRT group and 21 in the nICT group. There were no significant differences between the 2 groups in the baseline data. In the nCRT group, leukopenia occurred more often than in the nICT group, and hemoglobin-decreasing events were rarer (P=0.03<0.05). A significantly higher proportion of patients in the nICT group experienced erythema following neoadjuvant therapy compared to the nCRT group (23.81% vs. 0%; P=0.01<0.05). Neoadjuvant therapy showed no significant difference between the 2 groups for adverse event rates, surgery-related indicators, postoperative pathological remission rates, and postoperative complications. Conclusions: nICT was a safe and feasible treatment for locally advanced ESCC and it may be a potential new treatment modality.

A revamped MIC-McKeown operation without removing azygos vein arch, bronchial artery and vagus nerve trunk.

BACKGROUND: The purpose of this study was to investigate the effect of our revamped MIE-McKeown operation on postoperative gastrointestinal function recovery. METHODS: This revamped MIE-McKeown operation without removing azygos vein arch, bronchial artery and vagus nerve trunk and with the tubular stomach buried throughout esophageal bed and azygos arch, has been implemented from July 2020 to July 2021 by the same medical team of Gaozhou People's Hospital thoracic surgery for 13 times. Preoperative clinical data, main intraoperative indicators and postoperative complications were observed. RESULTS: All patients had esophageal malignant tumors at the level of middle and lower thoracic non-azygous venous arch, with preoperative clinical stage CT1-2N0M0 stage i-ii. V-vst test was performed on the 7th postoperative day, and 10 patients were found to have no loss of safety/efficacy. There were 2 cases with impaired efficacy and no impaired safety, 1 case with impaired safety. There were 1 cases of pulmonary infection, 1 cases of anastomotic fistula combined with pleural and gastric fistula, 2 cases of hoarseness, 2 cases of arrhythmia, 10 cases of swallowing function were grade i, 2 cases of swallowing function were grade iii, 1 case of swallowing function was grade iv in watian drinking water test one month after operation. CONCLUSIONS: Merit of this revamped MIE-McKeown operation is well preserving the integrity of azygos arch of vagus nerve and bronchial artery, and it is technically safe and feasible. No postoperative mechanical obstruction of thoracostomach, huge thoracostomach and gastrointestinal dysfunction occurs.

Mining Database to Identify Aging-Related Molecular Subtype and Prognostic Signature in Lung Adenocarcinoma.

Background: Lung cancer is emerging as one of most deadly diseases, and the mortality rate was still high with 5-year overall survival rate less than 20%. Aging is referred as protumorigenic state, and it plays a significant role in cancer development. Methods: Molecular subtype of lung cancer was identified by consensus cluster analysis. Prognostic signature was constructed using LASSO cox regression analysis. CeRNA network was constructed to explore lncRNA-miRNA-mRNA regulatory axis. Results: A total of 27 differentially expressed aging-related genes (ARGs) were obtained in LUAD. Three clusters of TCGA-LUAD patients with significant difference in prognosis, immune infiltration, chemotherapy, and targeted therapy were identified. We also developed an aging-related prognostic signature that had a better performance in predicting the1-year, 3-year, and 5-year overall survival of LUAD. Further analysis suggested a significant correlation between prognostic signature gene expression and clinical stage, immune infiltration, tumor mutation burden, microsatellite instability, and drug sensitivity. We also identified the lncRNA UCA1/miR-143-3p/CDK1 regulatory axis in LUAD. Conclusion: Our study identified three clusters of TCGA-LUAD patients with significant difference in prognosis, immune infiltration, chemotherapy, and targeted therapy. We also developed an aging-related prognostic signature that had a good performance in the prognosis of LUAD.

Modified McKeown vs. traditional McKeown minimally invasive esophagectomy in improving short-term efficacy and the quality of life of esophageal cancers: a retrospective comparative cohort study.

Background: Traditional McKeown minimally invasive esophagectomy (MIE-McKeown) with resection of the thoracic and abdominal branches of vagus nerve, the azygos vein and the bronchial artery, is notorious for high complications incidence and sharply decreased quality of life (QoL) postoperatively in esophageal cancer (EC). Recently, reports of preservation of azygos vein arch or the vagus nerve have shown the advantages of decreasing postoperative complication incidence. However, the modified MIE-McKeown with preservation of azygos vein arch, vagus nerve and the bronchial artery has never been investigated in EC. In the present study, we aimed to compare the short-term efficacy and postoperative QoL between modified MIE-McKeown and traditional MIE-McKeown. Methods: A total of 218 eligible patients with esophageal squamous cell carcinoma (ESCC) who met our inclusion criteria between October 2018 and January 2022 in our center were retrospectively enrolled and divided into modified MIE-McKeown group (N=48) and the control group with traditional MIE-McKeown (N=170) according to their surgical procedure. We compared the perioperative parameters (e.g., operation time and postoperative complications) between the two groups. The core quality of life questionnaire (QLQ-C30) (version 3.0) and the EC-specific QoL assessment form (QLQ-OES18) were used to evaluate the QoL in the 2 groups at 1 and 3 months after operation. Results: There were no significant differences in baseline characteristics between modified MIE-McKeown group and the control group. Compared with the control group, the modified MIE-McKeown group had significantly lower postoperative drainage volume (551.46±249.45 vs. 812.96±405.82; P<0.001) and a lower incidence of thoracic stomach syndrome (TSS; P=0.001). The bleeding loss in the modified MIE-McKeown group was lower than that in the control group (56.88±20.44 vs. 83.18±97.93; P=0.066), but not significantly. There were no significant differences observed in postoperative complications and other perioperative parameters between the two groups. The results of QLQ-C30 and QLQ-OES18 questionnaire revealed that the modified MIE-McKeown group was associated with better physical function, better global health status and milder symptoms of gastroesophageal reflux and cough. Conclusions: The modified MIE-McKeown is a safe and efficient procedure and has the potential to improve postoperative health status of patients with EC.

Circ_0001273 downregulation inhibits the growth, migration and glutamine metabolism of esophageal cancer cells via targeting the miR-622/SLC1A5 signaling axis.

BACKGROUND: Esophageal cancer is a relatively rare cancer. However, its death rate is not to be taken lightly. Accumulating evidence indicates circular RNA (circRNA) is implicated in cancer development. The objective of this study was to unveil the role of circ_0001273 in esophageal cancer (EC). METHODS: For expression analysis of circ_0001273, miR-622 and solute carrier family 1 member 5 (SLC1A5), quantitative real-time PCR (qPCR) and Western blot were conducted. Cell proliferation was evaluated by cell counting kit-8 (CCK-8), EdU and colony formation assays. Cell apoptosis and cell migration were investigated using flow cytometry assay and wound healing assay. Glutamine metabolism was assessed by glutamine consumption and glutamate production using matched kits. The predicted binding relationship between miR-622 and circ_0001273 or SLC1A5 was validated by dual-luciferase reporter assay. An in vivo xenograft model was established to determine the role of circ_0001273 on tumor growth. RESULTS: Circ_0001273 was upregulated in EC tumor tissues and cells. Knockdown of circ_0001273 repressed EC cell proliferation, migration, epithelial-mesenchymal transition (EMT) and glutamine metabolism. Circ_0001273 knockdown also blocked tumor development in animal models. MiR-622 was targeted by circ_0001273, and its inhibition reversed the functional effects of circ_0001273 knockdown. SLC1A5 was a target gene of miR-622, and circ_0001273 targeted miR-622 to positively regulate SLC1A5 expression. The inhibitory effects of miR-622 enrichment on EC cell proliferation, migration, EMT and glutamine metabolism were recovered by SLC1A5 overexpression. CONCLUSION: Circ_0001273 high expression contributed to EC progression via modulating the miR-622/SLC1A5 signaling axis.

Identification of the pyroptosis­related prognostic gene signature and the associated regulation axis in lung adenocarcinoma.

Lung adenocarcinoma (LUAD) remains the most common deadly disease and has a poor prognosis. Pyroptosis could regulate tumour cell proliferation, invasion, and metastasis, thereby affecting the prognosis of cancer patients. However, the role of pyroptosis-related genes (PRGs) in LUAD remains unclear. In our study, comprehensive bioinformatics analysis was performed to construct a prognostic gene model and ceRNA network. The correlations between PRGs and tumour-immune infiltration, tumour mutation burden, and microsatellite instability were evaluated using Pearson's correlation analysis. A total of 23 PRGs were upregulated or downregulated in LUAD. The genetic mutation variation landscape of PRG in LUAD was also summarised. Functional enrichment analysis revealed that these 33 PRGs were mainly involved in pyroptosis, the NOD-like receptor signalling pathway, and the Toll-like receptor signalling pathway. Prognosis analysis indicated a poor survival rate in LUAD patients with low expression of NLRP7, NLRP1, NLRP2, and NOD1 and high CASP6 expression. A prognostic PRG model constructed using the above five prognostic genes could predict the overall survival of LUAD patients with medium-to-high accuracy. Significant correlation was observed between prognostic PRGs and immune-cell infiltration, tumour mutation burden, and microsatellite instability. A ceRNA network was constructed to identify a lncRNA KCNQ1OT1/miR-335-5p/NLRP1/NLRP7 regulatory axis in LUAD. In conclusion, we performed a comprehensive bioinformatics analysis and identified a prognostic PRG signature containing five genes (NLRP7, NLRP1, NLRP2, NOD1, and CASP6) for LUAD patients. Our results also identified a lncRNA KCNQ1OT1/miR-335-5p/NLRP1/NLRP7 regulatory axis, which may also play an important role in the progression of LUAD. Further study needs to be conducted to verify this result.

The intra-class heterogeneity of immunophenotyping and immune landscape in oesophageal cancer and clinical implications.

BACKGROUND: The response rate and survival benefit of immunotherapy vary among patients, implying specific immune status of an individual could be associated with the effect of immunotherapy. However, in-depth studies of immune subtypes (ISs), immune landscape and tumour microenvironment of oesophageal cancer (ESCA) and their clinical implications are less reported. METHODS: We first accessed data from publicly available databases and preprocessed it based on a standard protocol. Then, ISs were identified by unsupervised learning. Thereafter, the association of these ISs and tumour mutation burden (TMB), biomarkers of chemotherapy-induced immune response, tumour markers were also assessed. In addition, the immune characteristics, immune landscape, co-expression network of immune genes, and clinical implications were visualized and analysed. RESULTS: We identified three immunoclusters based on immune-associated genes with intra-class heterogeneity and prognostic value. Cluster-specific associations with TMB, markers of chemotherapy-induced immune response, and tumour markers were revealed. A 4-gene signature (risk score= -0.16514291×BHLHE22-0.03964046×MXRA8-0.15242778×SLIT2-0.05553572×SPON1) based on co-expressed genes in the immunoclusters was developed and externally validated. CONCLUSIONS: In summary, we identified clinically relevant immunoclusters in both adenocarcinoma and squamous cell carcinoma of oesophagus, revealing the necessity of assessing the complexity and diversity of immune microenvironment for cancer immunotherapy.

A propensity score matching study of the short-term efficacy of azygos arch-sparing McKeown minimally invasive esophagectomy.

BACKGROUND: To evaluate the short-term efficacy of azygos arch-sparing McKeown minimally invasive esophagectomy (McKeown-MIE). METHODS: We retrospectively analyzed the clinical data of 221 patients with thoracic esophageal squamous cell carcinoma who underwent McKeown-MIE at the Department of Thoracic Surgery of Gaozhou People's Hospital from August 1, 2017 to September 30, 2019. According to whether the azygos arch was preserved or not, the patients were assigned to one of two groups: the preservation group (40 cases) and the ligation group (181 cases). Within 3 months of the operation, the perioperative outcomes and the postoperative short-term efficacy of the two groups were compared. RESULTS: After propensity score (PS) matching, 40 pairs of patients were matched successfully. Between the two groups, there were no statistical difference in intraoperative blood loss, the number of lymph nodes dissected, thoracic drainage duration, fasting time, postoperative hospital stay time, and major postoperative complications (P>0.05). Compared with the ligation group, patients in the preservation group had a shorter intensive care unit (ICU) stay time, a shorter operative time, a lower volume of postoperative thoracic drainage (both the first 3 days and overall) following surgery, a tubular stomach that had a smaller caliber, and a lower incidence of tubular gastric malpositioning (P<0.05). CONCLUSIONS: Preserving the azygos arch during a McKeown-MIE is safe and feasible. Doing so, not only effectively restricts the expansion of the gastric conduit, leading to a lower incidence of malpositioning, but also dramatically reduces postoperative thoracic drainage, and ICU stay time.