Transcervical inflatable mediastinoscopic esophagectomy versus thoracoscopic esophagectomy for local early- and intermediate-stage esophageal squamous cell carcinoma: A propensity score-matched analysis.

BACKGROUND AND OBJECTIVE: Transcervical inflatable mediastinoscopic esophagectomy (TIME) is a novel method of minimally invasive esophagectomy (MIE) for esophageal cancer. However, whether TIME is effective and feasible as conventional MIE remains unclear. This study aimed to evaluate the efficacy of TIME by comparing it with thoracoscopic esophagectomy (TE). METHODS: Surgical outcomes and relapse-free survival (RFS) rates of patients with local early- or intermediate-stage thoracic esophageal squamous cell carcinoma that underwent TIME or TE from January 2017 to December 2019 were analyzed in this retrospective study. Propensity score matching was used to control the confounding factors. RESULTS: The mean operation time in TIME was shorter than that in TE (p < 0.05). Patients in the TIME group achieved postoperative ambulation earlier than those in the TE group (p < 0.05). The rate of pulmonary complications was lower in TIME than in TE (p < 0.05). The number of lymph nodes harvested during surgery and the RFS rates of two groups did not have significant differences. CONCLUSION: TIME may be a feasible and safe method to treat local early- and intermediate-stage thoracic esophageal squamous cell carcinoma effectively and it could be a supplementary surgical method of TE for patients with poor pulmonary function or cannot undergo TE.

Ubiquitination of NOTCH2 by DTX3 suppresses the proliferation and migration of human esophageal carcinoma.

The NOTCH2 gene plays a role in the development of many tumors. Deltex E3 ubiquitin ligase 3 (DTX3) was identified as a novel E3 ligase for NOTCH2 and as a potential therapeutic target for esophageal cancer. However, whether DTX3 could regulate NOTCH2 to suppress the progression of esophageal carcinoma remains unknown. In our study, NOTCH2 had higher expression in human esophageal carcinoma cell lines compared to normal human esophageal epithelial cell line, and ablation of NOTCH2 suppressed the proliferation and migration of esophageal carcinoma cells. A novel E3 ligase for NOTCH2 was identified by yeast two-hybrid (Y2H) screening, and DTX3 promoted the ubiquitination and degradation of NOTCH2. Further study showed that DTX3 overexpression suppressed the proliferation and tumorigenicity of human oesophageal carcinoma cells. The analysis of tissue samples from patients revealed that the expression of NOTCH2 was high while the expression of DTX3 was low in esophageal cancer. Furthermore, the expression of DTX3 and NOTCH2 showed a significant negative correlation in human oesophageal cancer samples. Our study suggested that the DTX3-NOTCH2 axis plays an important role in the progression of esophageal cancer, and DTX3 acts as an anti-oncogene in esophageal carcinoma, potentially offering a therapeutic target for esophageal cancer.

A preliminary study of modified inflatable mediastinoscopic and single-incision plus one-port laparoscopic esophagectomy.

Background: Esophageal malignancies have a high morbidity rate worldwide, and minimally invasive surgery has emerged as the primary approach for treating esophageal cancer. In recent years, there has been increasing discussion about the potential of employing inflatable mediastinoscopic and laparoscopic approaches as an option for esophagectomy. Building on the primary modification of the inflatable mediastinoscopic technique, we introduced a secondary modification to further minimize surgical trauma. Methods: We conducted a retrospective analysis of patients who underwent inflatable mediastinoscopy combined with laparoscopic esophagectomy at the Second Affiliated Hospital of Naval Medical University from March 2020 to March 2023. The patients were allocated to the following two groups: the traditional (primary modification) group, and the secondary modification group. Operation times, intraoperative bleeding, and postoperative complications were compared between the groups. Results: The procedure was successfully performed in all patients, and conversion to open surgery was not required in any case. There were no statistically significant differences in the surgical operation time, intraoperative bleeding, number of dissected lymph nodes, and rate of postoperative anastomotic leakage between the two groups. However, a statistically significant difference was observed in the length of the mobilized esophagus between the two groups. The mobilization of esophagus to the level of diaphragmatic hiatus via the cervical incision was successfully achieved in more patients in the secondary modification group than the primary modification group. Conclusions: Inflatable mediastinoscopy combined with single-incision plus one-port laparoscopic esophagectomy is a safe and effective surgical procedure. The use of a 5-mm flexible endoscope, ultra-long five-leaf forceps, and LigaSure Maryland forceps facilitates esophageal mobilization and lymph node dissection through a single cervical incision.

Application of wireless thoracoscopy in thoracic surgery.

To explore the safety and feasibility of wireless thoracoscope in thoracic surgery. A retrospective analysis was made of all the clinical data of 90 patients with thoracoscope lung resection, from April to August 2021, Shanghai changzheng hospital thoracic minimally invasive center. Compared the thoracoscope preparation time, picture resolution, picture delay, surgeon comfort level, assistant comfort level between the wireless thoracoscope group and wired thoracoscope group. The thoracoscopic preparation time of the wireless thoracoscope group was significantly shorter than that of the wired group (26.66 ± 6.04 vs 62.14 ± 10.07, p < 0.0001). Comfort level of the surgeon (4.64 ± 0.48 vs 3.77 ± 0.42, p < 0.001) and the comfort level of the assistant (4.85 ± 0.36 vs 3.88 ± 0.32, p < 0.001) of the wireless thoracoscope group were higher than that of the wired thoracoscope group. There were no statistically significant differences in video sharpness (4.64 ± 0.48 vs 4.74 ± 0.44, p = 0.31). Although there was one case picture delay in wireless group, it was caused by low power which could be dealt with by a good charge before surgery. The wireless thoracoscope has the advantages of short preparation time, high comfort for the surgeon and the assistant, no less than the wired thoracoscope in picture resolution and picture delay. Wireless connection is more convenient and portability, which is worthy of further application in clinical practice.

A new preoperative localization of pulmonary nodules guided by mixed reality: a pilot study of an animal model.

Background: With the popularity of high-resolution computed tomography (HRCT), more and more pulmonary nodules are being discovered. Video-assisted thoracoscopic surgery (VATS) has become the first choice for surgical treatment of pulmonary nodules. The use of accurate preoperative localization is crucial for successful resection in VATS. At present, there are many kinds of preoperative localization methods, but there are certain disadvantages. This study aimed to evaluate the feasibility and safety of mixed reality (MR)-guided pulmonary nodules localization, which is a new method that can benefit patients to a greater extent. Methods: By constructing an animal model of pulmonary nodules localization, 28 cases of pulmonary nodules were located by MR-guided localization. We recorded the localization accuracy, localization time, insertion attempts, and incidence of complications related to localization under MR-guidance. Results: All 28 nodules were successfully located: the deviation of MR-guided localization was 5.71±2.59 mm, localization time was 8.07±1.44 min, and insertion attempts was 1. A pneumothorax and localizer dislodgement occurred in 1 case, respectively. Conclusions: Since preoperative localization is critical for VATS resection of pulmonary nodules, we investigated a new localization method. As indicated by our study, MR-guided localization of pulmonary nodules is feasible and safe, which is worthy of further research and promotion. We have also registered corresponding clinical trials to further investigate and help to improve our understanding of this technique.

Effect Evaluation of Subxiphoid and Intercostal Thymectomy: A Meta-Analysis and Systematic Review.

Background: It still remains unclear whether subxiphoid video-assisted thoracoscopic surgery (SVATS) thymectomy is safe and reasonable. This meta-analysis aims at assessing the effectiveness and safety of SVATS for thymoma in comparison with that of intercostal video-assisted thoracoscopic surgery (IVATS) thymectomy. Methods: All the relevant data systematically analyzed in this thesis were retrieved from PubMed, the Cochrane Library, web of science, EMBASE, and ClinicalTrials.gov. The time span for data retrieval was from the date of database establishment to March 2022. The outcome indicators include operation time, intraoperative blood loss, duration of postoperative drainage, postoperative hospital days, visual analogue scale (VAS) score on the day of operation, VAS score on postoperative day 3, and VAS score on postoperative day 7; postoperative complications were analyzed in our meta-analysis. Results: In 13 studies of this paper, there were 1,198 cases included. Among them, 563 cases were treated by SVATS thymectomy and 635 cases by IVATS thymectomy. There was no significant difference in the operation time [113.38 vs. 119.91  min, 95% confidence interval (CI): -0.70-0.15, p = 0.20) and the incidence of intraoperative and postoperative complications (RR = 0.82, 95% CI: 0.58-1.15, p = 0.25) between SVATS thymectomy and IVATS thymectomy. However, SVATS thymectomy significantly reduced the amount of intraoperative blood loss (47.68 vs. 66.69  mL, SMD = -0.57, 95% CI: -0.95 to -0.18, p = 0.004), postoperative drainage days (2.12 vs. 2.72 days, SMD = -0.46, 95% CI: -0.74 to -0.18, p = 0.001), postoperative hospital stays (4.53 vs. 5.91 days, SMD = -0.64, 95% CI: -0.96 to -0.31, p = 0.0001), and VAS scores after the operation. Discussion: SVATS thymectomy is safe and feasible, and the perioperative effect is better than IVATS thymectomy to a certain extent, which is worthy of popularization and further research.Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/.

Comprehensive analysis of transcriptome-wide m6A methylome in intermediate-stage Esophageal squamous cell carcinoma.

N6-Methyladenosine (m6A) RNA methylation is the most prevalent post-transcriptional modification mechanism in humans and plays an important role in the pathogenesis of various tumors. However, the investigation of m6A modification in Esophageal squamous cell carcinoma (ESCC) remains in its infancy. Transcriptome-wide m6A changes were profiled using human m6A epitranscriptomic microarrays in ESCC tissues and adjacent normal tissues. Differentially m6A-methylated mRNAs, lncRNAs and Mid-size ncRNAs were identified, followed by functional enrichment analysis. Moreover, we also establish a competing endogenous RNA (ceRNA) network based on the m6A-related lncRNA growth arrest specific 5 (GAS5) specific transcript（NR_152533）. The results suggested that RALYL may be a target gene for miR-3912-5p, and that GAS5 regulated RALYL expression by binding to miR-3912-5p.

A New Traceless Technique for Cosmetic Closure of Minimally Invasive Incision and Chest Tube Fixation After Uniportal Video-Assisted Thoracoscopic Surgery.

Background: With uniportal video-assisted thoracoscopic surgery (VATS) becoming mainstream, how to make the incision cosmetic has attracted much attention. This study aimed to introduce a new traceless method for cosmetic closure of the incision and a special procedure for chest tube fixation after uniportal VATS and to evaluate the feasibility, effectiveness, and safety of this new technique. Methods: In this retrospective study, a total of 258 consecutive patients who underwent uniportal VATS were included. Among them, 127 patients were treated with a conventional method, and 131 patients were treated with a new method. Results: Patients in the new method group had a significantly less incidence of subcutaneous emphysema after the chest tube was removed. The incidence of pneumothorax after the chest tube was removed and fat liquefaction of chest incision was not significantly different between the two groups. No differences in the incidence of pneumothorax after chest tube removal and fat liquefaction of postsurgical incision were found between the two groups. Additionally, there was also no significant difference in follow-up items. Conclusions: Taken together, our results showed that this new method for minimally invasive incision closure and chest tube fixation after uniportal VATS was as feasible, effective, and safe as the conventional one but more cosmetic.

Clinical comparative study of glasses-free 3D and 2D thoracoscopic surgery in minimally invasive esophagectomy.

Objective: To investigate the safety and efficacy of glasses-free three-dimensional (3D) thoracoscopic surgery in minimally invasive esophagectomy (MIE). Methods: The clinical data of 98 patients, including 81 men and 17 women aged 45-77 years, with esophageal squamous cell carcinoma who underwent minimally invasive thoracoscopic esophagectomy from January 2017 to December 2019 [3 years, with clinical follow-up time: 1 year~4 years (2017.01-2020.12)] were retrospectively analyzed. Patients were divided into two groups according to different surgical methods including a glasses-free 3D thoracoscopic group (G-3D group: 38 patients) and a two-dimesional (2D) thoracoscopic group (2D group: 60 patients). The clinical outcome of the two groups were compared. Results: The operation time of the thoracoscopic part in the G-3D group was significantly shorter than that in the 2D group (P<0.05). The total number of lymph node dissection in the G-3D group was more than that in the 2D group (P<0.05). The thoracic indwelling time, postoperative hospital stay, severe pulmonary infection, arrhythmia, anastomotic leakage, chylothorax, and recurrent laryngeal nerve injury were not significantly different between the two groups (P>0.05). There was also no significant difference between the two groups on the progression-free survival (P>0.05). Conclusion: Glasses-free 3D thoracoscopic surgery for esophageal cancer is a safe and effective surgical procedure. Compared with 2D thoracoscopic MIE, glasses-free 3D thoracoscopic MIE for esophageal cancer has higher safety, more lymph node dissection, and higher operation efficiency through the optimized surgical operations. We believe that glasses-free 3D thoracoscopy for MIE is worthy of clinical promotion.

Comparative study on short-term efficacy of single incision plus one (SI+1) port and multiportal 3D laparoscopic minimally invasive esophagectomy.

BACKGROUND: To evaluate the safety and efficacy of single incision plus one (SI+1) port three-dimensional (3D) laparoscopic minimally invasive esophagectomy (MIE). METHODS: Clinical data of patients who underwent 3D thoracic laparoscopic MIE in our department from September 2020 to March 2021 were analyzed retrospectively. According to the different methods of laparoscopic surgery, the patients were divided into 2 groups: SI+1 port 3D laparoscopy group and multiportal 3D laparoscopy group. The operation time of the 3D laparoscopy component, amount of intraoperative blood loss, number of celiac lymph node dissections, postoperative abdominal drainage days, postoperative total abdominal drainage, postoperative complications, and length of hospital stay were analyzed. RESULTS: There was no significant difference between the 2 methods in laparoscopic operation time (30.11±5.86 vs. 28.45±4.72 min, P=0.49), intraoperative blood loss (34.44±9.82 vs. 35.91±6.25 mL, P=0.69), number of celiac lymph node dissections (8.44±3.13 vs. 7.09±2.12, P=0.27), postoperative abdominal drainage days (3.11±0.33 vs. 3.00±0.00 days, P=0.28), postoperative total abdominal drainage (95.00±23.33 vs. 92.27±11.26 mL, P=0.74), postoperative complications (22.2% vs. 27.3%, P=0.33), and hospital stay (9.67±0.71 vs. 10.18±0.87 days, P=0.17). None of the patients enrolled in the study had recurrence or death to date. CONCLUSIONS: The application of SI+1 port 3D laparoscopy in minimally invasive resection of esophageal carcinoma is safe and feasible.

Three-dimension versus two-dimension video-assisted thoracoscopic surgery for esophageal cancer: a meta-analysis.

BACKGROUND: It still remains unclear whether three-dimension (3D) video-assisted thoracoscopic surgery (VATS) for esophageal cancer is safe and reasonable. This meta-analysis aims at assessing the effectiveness and safety of 3D VATS for esophageal cancer in comparison with that of two-dimension (2D) VATS. METHODS: All the relevant data systematically analyzed in this thesis is from PubMed, Embase, The Cochrane Library, Web of Science and clinicaltrials.gov, and the time span for retrieval is from the date of the database establishment to February 2021. The research on the efficacy and safety of 3D VATS for esophageal cancer and 2D VATS is consistent with our meta-analysis. Continuous variables and dichotomy variables are compared using odds ratio, average or standard average differences with 95% confidence interval (95% CI), and P values, respectively. RESULTS: In five studies of this paper, there were 553 patients in total (3D VATS group, n=266 and 2D VATS group, n=287). Patients in the 3D group had shorter operation time [standardized mean difference (SMD) =-0.99, 95% CI: -1.66 to -0.32; P=0.004], and less bleeding (SMD =-0.88, 95% CI: -1.66 to -0.10; P=0.03) than those in the 2D group. The total amount of dissected lymph node and post-operative complications in the 2D group and the 3D group were nearly the same, showing no significant difference. DISCUSSION: The results of this meta-analysis showed that 3D VATS for esophageal cancer will be more applied and developed in the future. REGISTRATION NUMBER OF PROSPERO: CRD42021238863.

Intra-operative events and countermeasures during esophagectomy via transcervical incision inflatable single-port mediastinoscope combined with laparoscopy.

BACKGROUND: Esophagectomy via transcervical incision inflatable single-port mediastinoscope combined with laparoscopy as a safe and feasible minimally invasive technique has gained attention recently. But the occurrence of Intraoperative events is inevitable. It's necessary to investigate and discuss the intraoperative events and countermeasures during operation. METHODS: Intraoperative events were retrospectively reviewed in 60 patients who underwent esophagectomy via transcervical incision inflatable single-port mediastinoscope combined with laparoscopy in the recent 3 years. RESULTS: There was no perioperative death and no aortic or bronchial injury. Bronchial artery injury occurred in 2 cases (3.34%), bronchial artery combined with azygos vein hemorrhage occurred in 1 case (1.67%). The pleura were injured in 3 cases (5%). Recurrent laryngeal nerve injury was noticed in 7 cases (11.67%). Thoracic duct injury occurred in 1 case (1.67%). CONCLUSIONS: As a new surgical method, esophagectomy via transcervical incision inflatable single-port mediastinoscope combined with laparoscopy is considered safe and feasible, but requires improvement when compared with traditional surgical methods. Due to the influence of surgical space and with experienced surgeons, the incidence of intraoperative events such as intraoperative bleeding and thoracic duct injury is not dominant when compared with the traditional surgical methods. Thoracic surgeons should continuously improve their clinical knowledge as well as skills. Careful preoperative examination and evaluation of the patients, being familiar with the anatomical structure and various methods, wise selection of energy devices and calmly dealing with all kinds of events are the key factors for successful surgeries with fewer intraoperative events.

E3 ligase MKRN3 is a tumor suppressor regulating PABPC1 ubiquitination in non-small cell lung cancer.

Central precocious puberty (CPP), largely caused by germline mutations in the MKRN3 gene, has been epidemiologically linked to cancers. MKRN3 is frequently mutated in non-small cell lung cancers (NSCLCs) with five cohorts. Genomic MKRN3 aberrations are significantly enriched in NSCLC samples harboring oncogenic KRAS mutations. Low MKRN3 expression levels correlate with poor patient survival. Reconstitution of MKRN3 in MKRN3-inactivated NSCLC cells directly abrogates in vitro and in vivo tumor growth and proliferation. MKRN3 knockout mice are susceptible to urethane-induced lung cancer, and lung cell-specific knockout of endogenous MKRN3 accelerates NSCLC tumorigenesis in vivo. A mass spectrometry-based proteomics screen identified PABPC1 as a major substrate for MKRN3. The tumor suppressor function of MKRN3 is dependent on its E3 ligase activity, and MKRN3 missense mutations identified in patients substantially compromise MKRN3-mediated PABPC1 ubiquitination. Furthermore, MKRN3 modulates cell proliferation through PABPC1 nonproteolytic ubiquitination and subsequently, PABPC1-mediated global protein synthesis. Our integrated approaches demonstrate that the CPP-associated gene MKRN3 is a tumor suppressor.

A novel scoring system predicts postsurgical survival and adjuvant chemotherapeutic benefits in patients with pancreatic adenocarcinoma: Implications for AJCC-TNM staging.

BACKGROUND: We evaluated the application of the latest 8th American Joint Committee on Cancer (AJCC) staging system in Chinese patients and determined whether the addition of biologic markers could improve the prediction of postsurgical survival in pancreatic adenocarcinoma (PC). METHODS: This multicenter study involved 1,223 consecutive patients who underwent margin-negative pancreatectomy for PC. A scoring system was devised based on AJCC pathologic parameters and biologic markers and defined using a Cox proportional hazards model. Prognostic accuracies were evaluated by concordance index (C-index) and Akaike information criterion (AIC). RESULTS: The 8th edition AJCC staging system had a better survival distribution of PC with different stages and a similar C-index (0.62 in the training cohort, 0.60 in the validation cohort) than the 7th edition (0.59 in the training cohort, 0.58 in the validation cohort). Nevertheless, survival of resected patients with stage IIA or IIB disease was indistinguishable. Incorporation of postoperative carbohydrate antigen 19-9 (CA19-9) levels and tumor grade into the 8th edition AJCC staging system generated a scoring system with better predictive accuracy for overall survival (OS) (C-index of 0.73 and AIC of 4301.05 in the training cohort, C-index of 0.71 and AIC of 3309.23 in the validation cohort). More importantly, patients with median or higher scores experienced OS benefits from adjuvant chemotherapy. CONCLUSION: Postoperative CA19-9 levels and tumor grade are two well-known PC biologic markers that could be incorporated into a standard AJCC staging system to refine risk stratification and predict OS benefit from adjuvant chemotherapy in resected PC.