Comparison of pulmonary function changes between patients receiving neoadjuvant chemotherapy and chemoradiotherapy prior to minimally invasive esophagectomy: a randomized and controlled trial.

PURPOSE: Adequate pulmonary function is important for patients undergoing surgical resection of esophageal cancer, especially those that received neoadjuvant therapy. However, it is unknown if pre-operative radiation affects pulmonary function differently compared to chemotherapy. The purpose of this study was to compare changes in pulmonary function between patients undergoing minimally invasive esophagectomy (MIE) who received neoadjuvant chemotherapy or chemoradiotherapy. METHODS: Between March 2017 and March 2018, esophageal cancer patients requiring neoadjuvant therapy were prospectively enrolled and randomly assigned to receive chemotherapy (CT) or chemoradiotherapy (CRT) before MIE. All patients received pulmonary function testing before and after the neoadjuvant therapy. Changes in pulmonary function, operative data, and pulmonary complications were compared between the 2 groups. RESULTS: A total of 71 patients were randomized and underwent MIE after receiving CT (n = 34) or CRT (n = 37). Baseline clinical characteristics were comparable between the 2 groups. The CRT group experienced a greater decrease of forced expiratory volume at 1 s (FEV1) (2.66 to 2.18 L, p = 0.023) and diffusion capacity of the lung for carbon monoxide divided by the mean alveolar volume (DLCO/Va) (17.3%, p < 0.001) than the CT group (FEV1 2.53 to 2.41 L; DLCO/Va 4.8%). The incidence of pulmonary complications was higher in the CRT group (13.51 vs. 8.82%), but the difference was not significant (p = 0.532). CONCLUSIONS: Preoperative CRT affects pulmonary function more than CT alone, but does not increase the risk of pulmonary complications in patients undergoing MIE.

The effect of enhanced recovery after minimally invasive esophagectomy: a randomized controlled trial.

BACKGROUND: The purpose of this randomized controlled trial was to determine if enhanced recovery after surgery (ERAS) would improve outcomes for three-stage minimally invasive esophagectomy (MIE). METHODS: Patients with esophageal cancer undergoing MIE between March 2016 and August 2018 were consecutively enrolled, and were randomly divided into 2 groups: ERAS+group that received a guideline-based ERAS protocol, and ERAS- group that received standard care. The primary endpoint was morbidity after MIE. The secondary endpoints were the length of stay (LOS) and time to ambulation after the surgery. The perioperative results including the Surgical Apgar Score (SAS) and Visualized Analgesia Score (VAS) were also collected and compared. RESULTS: A total of 60 patients in the ERAS+ group and 58 patients in the ERAS- group were included. Postoperatively, lower morbidity and pulmonary complication rate were recorded in the ERAS+ group (33.3% vs. 51.7%; p = 0.04, 16.7% vs. 32.8%; p = 0.04), while the incidence of anastomotic leakage remained comparable (11.7% vs. 15.5%; p = 0.54). There was an earlier ambulation (3 [2-3] days vs. 3 [3-4] days, p = 0.001), but comparable LOS (10 [9-11.25] days vs. 10 [9-13] days; p = 0.165) recorded in ERAS+ group. The ERAS protocol led to close scores in both SAS (7.80 ± 1.03 vs. 8.07 ± 0.89, p = 0.21) and VAS (1.74 ± 0.85 vs. 1.78 ± 1.06, p = 0.84). CONCLUSIONS: Implementation of an ERAS protocol for patients undergoing MIE resulted in earlier ambulation and lower pulmonary complications, without a change in anastomotic leakage or length of hospital stay. Further studies on minimizing leakage should be addressed in ERAS for MIE.

CircCDR1 sponges miR-1290 to regulate cell proliferation, migration, invasion, and apoptosis in esophageal squamous cell cancer.

Since circCDR1 was abnormally expressed in esophageal squamous cell cancer (ESCC), the current study explored whether circCDR1 affected ESCC. Detailedly, circCDR1 expression in ESCC and linear isoform and stability of circCDR1 were detected by RT-qPCR. The location of circCDR1 was detected by fluorescence in situ hybridization (FISH). After transfection, the cell biological functions were detected by wound-healing, CCK-8, colony formation, and flow cytometry assays. The target of circCDR1 was predicted by bioinformatics, FISH, RNA pull-down, and dual-luciferase reporter assays. The correlation between circCDR1 and miR-1290 was analyzed by Pearson's correlation analysis. A subcutaneous-xenotransplant tumor model in BALB/c nude mice was established and the levels of circCDR1, miR-1290, and apoptosis/metastasis/proliferation-related factors in the cancer cells and tissues were detected by immunohistochemical analysis, western blot, or RT-qPCR. As a result, circCDR1 was low-expressed in ESCC tissues and cells, while miR-1290 was high-expressed. CircCDR1 was regulated and was negatively correlated with miR-1290. CircCDR1, located in cytoplasm, inhibited the viability, proliferation, migration, and invasion of the cancer cells and the expressions of Bcl-2, N-cadherin, and Vimentin, but enhanced cell apoptosis and the expressions of C caspase-3, Bax, E-cadherin, IGFBP4, LHX6 and NFIX. In vivo, circCDR1 promoted xenotransplanted tumor weight and volume, and the expressions of C caspase-3 and Bax yet suppressed the levels of Bcl-2, miR-1290, and Ki-67 in tumor tissues. The effects of circCDR1 on both cancer cells and tissues were opposite to and reversed by miR-1290 mimic. Collectively, circCDR1 sponged miR-1290 to regulate the progression of ESCC both in vitro and in vivo.

circPOLR1C Promotes the Development of Esophageal Cancer by Adsorbing miR-361-3p and Regulating Cancer Cell Apoptosis and Metastasis.

Background: The effect of circular RNA-RNA polymerase I and III subunit C (circPOLR1C) on esophageal cancer (EC) has not been reported. Herein, this study is designed to unveil the effect and the regulatory mechanism of circPOLR1C on EC. Methods: The expression of circPOLR1C in EC tissues and cells was detected by qRT-PCR. Circular structure, stability, and cell localization of circPOLR1C were confirmed by qRT-PCR, RNase R, actinomycin D, and fluorescence in situ hybridization (FISH) assay. Cell function experiments, nude mouse xenograft, lung transplant model, and HE staining were performed to evaluate the effects of CircPOLR1C on EC in vitro and in vivo. A regulatory relationship between miR-361-3p and circPOLR1C was confirmed by qRT-PCR, circRNA in vivo precipitation, RIP, FISH, CircInteractome database, dual-luciferase reporter assay, and immunohistochemistry. Rescue experiments were applied to assess the effects of miR-361-3p and circPOLR1C on EC cells and tissues. Apoptosis- and epithelial-mesenchymal transformation (EMT)-related gene expressions were quantified by qRT-PCR and Western blot. Results: Highly expressed circPOLR1C in EC was related to tumor differentiation and invasion. circPOLR1C, which mainly exists in the cytoplasm, is a stable circular RNA. circPOLR1C silencing inhibited circPOLR1C expression and EC cell malignant function, while circPOLR1C overexpression promoted the growth of transplanted tumors and lung metastasis. The enrichment of miR-361-3p was higher than that of other targeted miRNAs. circPOLR1C adsorbed miR-361-3p to regulate apoptosis- and EMT-related genes and partially reversed the tumor suppressive effect of miR-361-3p, which was lowly expressed in EC tissues. Silencing the target genes of miR-361-3p also inhibited the malignant development of EC cells. Conclusion: circPOLR1C adsorbs miR-361-3p and regulates apoptosis- and EMT-related gene expressions to promote the development of EC.

The predictive value of microRNAs for pathological response after neoadjuvant treatment in esophageal squamous cell carcinoma: a systematic review.

Neoadjuvant treatment followed by esophagectomy has been the standard strategy for resectable locally advanced esophageal squamous cell carcinoma (ESCC). Pathological response after neoadjuvant treatment is of vital importance in the determination of long-term survival. Due to the involvement of microRNAs (miRNAs) in ESCC, some studies have proposed miRNA models to predict the pathological response. We aimed to summarize current studies on the predictive value of the miRNA models. We searched the relevant studies on PubMed, Web of Science and Cochrane Library up to February 14, 2020, using the following search term: (esophageal OR esophagus OR oesophageal OR oesophagus) AND (miR OR miRNA OR microRNA) AND (neoadjuvant OR preoperative OR induction). The initial search retrieved 206 studies. We briefly summarized the involvement of miRNAs in the origin, development and chemo- and radioresistance in ESCC. Then, 9 studies were enrolled in the systematic review. A great heterogeneity was observed across these studies. Of the 6 studies with diagnostic tests, the area under curve varied a lot. Although much evidence demonstrated the correlation between miRNAs and pathological response after in ESCC, the current studies has not established any promising models. A well-designed prospective study is essential to investigate the potential predictive models for pathological response after neoadjuvant treatment in ESCC.

Transcervical minimally invasive esophagectomy: hemodynamic study on an animal model.

BACKGROUND: Transcervical esophagectomy is a less invasive procedure performed within mediastinum. However, the mediastinum offers limited surgical space and the surgery via this route differs from conventional minimally invasive esophagectomy. Therefore, the physiological study of this surgical approach on an animal model would be necessary before the procedure gained more popularity. METHODS: We conducted transcervical minimally invasive esophagectomy on animal model (swine) under CO2 pneumomediastinum. The hemodynamic parameters were monitored using float catheter cannulated via right jugular vein. At different anatomical level (the upper, middle, and lower thoracic part of the animal esophagus), increased artificial pneumomediastinal pressures (0, 4, 8, 12, and 16 mmHg) were consecutively allocated to record the intra-operative changes of blood pressure, cardiac output (CO), central venous pressure (CVP), pulmonary artery pressure (PAP) and extravascular lung water (EVLW). Meanwhile, the surgical field under different pneumomediastinum pressure was recorded and balanced with animals' hemodynamic changes to determine the optimal pressure for transcervical minimally invasive esophagectomy. RESULTS: The animal procedures were accomplished without conversions. During the upper thoracic stage, increased CO2 pressures did not lead to significant changes in hemodynamic parameters including the blood pressure, CO, CVP, PAP or the level of EVLW. During the middle thoracic stage, pneumomediastinum under 4-12 mmHg did not lead to significant changes in hemodynamic parameters. However, pneumomediastinum at 16 mmHg resulted in lower CO (P=0.038) when compared to 0-12 mmHg. During lower thoracic stage, as the pneumomediastinum pressures increased from 0 to 16 mmHg, significant decrease in CO (P=0.022), and increase in CVP (P=0.036) was recorded. In compared to 4 mmHg pneumomediastinum, the surgical field under 8-16 mmHg artificial CO2 pneumomediastinum was suitable for mediastinal manipulation. CONCLUSIONS: During transcervical minimally invasive esophagectomy on animal model, the mobilization of swine thoracic esophagus with optimal pneumomediastinum pressure 8-12 mmHg is safe and effective based on hemodynamic analysis.

Learning curve for uniportal video-assisted thoracoscopic surgery lobectomy-results from 120 consecutive patients.

BACKGROUND: Uniportal video-assisted thoracoscopic surgery (VATS) is considered a technically demanding procedure. The learning curve, which directly influences the adoption of uniportal VATS, has not been described. In this study, we aimed to describe the learning curve for uniportal VATS lobectomy from our single center's experience. METHODS: Uniportal VATS lobectomy was started in October 2013 in Zhongshan Hospital, Fudan University. Since then, a total of 120 consecutive patients who underwent uniportal VATS lobectomy were retrospectively enrolled. Surgical videos were reviewed to determine the operation time, to which cumulative sum (CUMSUM) method was applied to evaluate the learning phases of the procedure. Accordingly, patients' clinical features in different phases were collected and compared to determine the learning curve for uniportal VATS lobectomy. RESULTS: Among the 120 consecutive patients reviewed from October 2013 to September 2014, the CUMSUM curve showed its inflection at patient number 44: the first 30 patients were in the ascending phase, the second 30 patients were in the plateau phase, and the remaining patients were in the descending phase. Comparable CUMSUM results were recorded both from upper and not-upper lobectomy. Intra-operatively, more repeated stapler attempts (73% versus 13% and 5%, P<0.001) and higher conversion rate (17% versus 7% and 2%, P=0.028) were recorded in ascending phase vs. the plateau phase and descending phase, respectively. Post-operatively, the morbidity, mortality and the length of hospital stay were similar before and after the learning curve cases. CONCLUSIONS: In a center with conventional VATS experience, the learning period of uniportal VATS lobectomy was characterized by repeated stapler attempts, and the volume requirements would be approximately 30 cases to reach the performance plateau. Upper lobectomy seemed not more difficult to learn than lower or middle lobectomy in uniportal VATS.

Minimally invasive surgery for giant esophageal leiomyoma: a case report & review of the literatures.

Despite the rapid development of minimally invasive surgery, the treatment of esophageal lesions remains controversial. Giant esophageal leiomyoma could be removed once diagnosed, but its operative method is not quite the same as esophageal leiomyoma of small size. We report a case of giant esophageal leiomyoma and review published cases of giant leiomyomas in the past 10 years. A 29-year-old man was admitted to the clinic for the complaints of 2-month history of dysphagia and discomfort. Radiologic and endoscopic findings suggested esophageal lesion in the muscular layer. The VATS enucleation was performed to relieve the patient's symptoms. The patient started oral intake on the 1st postoperative day, with following solid meal. The postoperative course was uneventful, and the patient was discharged on the 8th postoperative day.