A Video-Based Procedure-Specific Competency Assessment Tool for Minimally Invasive Esophagectomy.

Importance: Minimally invasive esophagectomy (MIE) is a complex procedure with substantial learning curves. In other complex minimally invasive procedures, suboptimal surgical performance has convincingly been associated with less favorable patient outcomes as assessed by peer review of the surgical procedure. Objective: To develop and validate a procedure-specific competency assessment tool (CAT) for MIE. Design, Setting, and Participants: In this international quality improvement study, a procedure-specific MIE-CAT was developed and validated. The MIE-CAT contains 8 procedural phases, and 4 quality components per phase are scored with a Likert scale ranging from 1 to 4. For evaluation of the MIE-CAT, intraoperative MIE videos performed by a single surgical team in the Esophageal Center East Netherlands were peer reviewed by 18 independent international MIE experts (with more than 120 MIEs performed). Each video was assessed by 2 or 3 blinded experts to evaluate feasibility, content validity, reliability, and construct validity. MIE-CAT version 2 was composed with refined content aimed at improving interrater reliability. A total of 32 full-length MIE videos from patients who underwent MIE between 2011 and 2020 were analyzed. Data were analyzed from January 2021 to January 2023. Exposure: Performance assessment of transthoracic MIE with an intrathoracic anastomosis. Main Outcomes and Measures: Feasibility, content validity, interrater and intrarater reliability, and construct validity, including correlations with both experience of the surgical team and clinical parameters, of the developed MIE-CAT. Results: Experts found the MIE-CAT easy to understand and easy to use to grade surgical performance. The MIE-CAT demonstrated good intrarater reliability (range of intraclass correlation coefficients [ICCs], 0.807 [95% CI, 0.656 to 0.892] for quality component score to 0.898 [95% CI, 0.846 to 0.932] for phase score). Interrater reliability was moderate (range of ICCs, 0.536 [95% CI, -0.220 to 0.994] for total MIE-CAT score to 0.705 [95% CI, 0.473 to 0.846] for quality component score), and most discrepancies originated in the lymphadenectomy phases. Hypothesis testing for construct validity showed more than 75% of hypotheses correct: MIE-CAT performance scores correlated with experience of the surgical team (r = 0.288 to 0.622), blood loss (r = -0.034 to -0.545), operative time (r = -0.309 to -0.611), intraoperative complications (r = -0.052 to -0.319), and severe postoperative complications (r = -0.207 to -0.395). MIE-CAT version 2 increased usability. Interrater reliability improved but remained moderate (range of ICCs, 0.666 to 0.743), and most discrepancies between raters remained in the lymphadenectomy phases. Conclusions and Relevance: The MIE-CAT was developed and its feasibility, content validity, reliability, and construct validity were demonstrated. By providing insight into surgical performance of MIE, the MIE-CAT might be used for clinical, training, and research purposes.

The development and validation of pathological sections based U-Net deep learning segmentation model for the detection of esophageal mucosa and squamous cell neoplasm.

Background: Deep learning methods have demonstrated great potential for processing high-resolution images. The U-Net model, in particular, has shown proficiency in the segmentation of biomedical images. However, limited research has examined the application of deep learning to esophageal squamous cell carcinoma (ESCC) segmentation. Therefore, this study aimed to develop deep learning segmentation systems specifically for ESCC. Methods: A Visual Geometry Group (VGG)-based U-Net neural network architecture was utilized to develop the segmentation models. A pathological image cohort of surgical specimens was used for model training and internal validation, with two additional endoscopic biopsy section cohort for external validation. Model efficacy was evaluated across several metrics including Intersection over Union (IOU), accuracy, positive predict value (PPV), true positive rate (TPR), specificity, dice similarity coefficient (DSC), area under the receiver operating characteristic curve (AUC), and F1-Score. Results: Surgical samples from ten patients were analyzed retrospectively, with each biopsy section cohort encompassing five patients. Transfer learning models based on U-Net weights yielded optimal results. For mucosa segmentation, the in internal validation achieved 93.81% IOU, with other parameters exceeding 96% (96.96% accuracy, 96.45% PPV, 96.65% TPR, 98.41% specificity, 96.81% DSC, 96.11% AUC, and 96.55% F1-Score). The tumor segmentation model attained an IOU of 91.95%, along with other parameters surpassing 95% (95.90% accuracy, 95.62% PPV, 95.71% TPR, 97.88% specificity, 95.81% DSC, 94.92% AUC, and 95.67% F1-Score). In the external validation for tumor segmentation model, IOU was 59.86% for validation database 1 (72.74% for accuracy, 76.03% for PPV, 77.17% for TPR, 83.80% for specificity, 74.89% for DSC, 71.83% for AUC, and 76.60% for F1-Score), and 50.88% for validation cohort 2 (68.03% for accuracy, 59.02% for PPV, 66.87% for TPR, 78.48% for specificity, 67.44% for DSC, 64.68% for AUC, and 62.70% for F1-Score). Conclusions: The models exhibited satisfactory results, paving the way for their potential deployment on standard computers and integration with other artificial intelligence models in clinical practice in the future. However, limited to the size of study, the generalizability of models is impaired in the external validation, larger pathological section cohort would be needed in future development to ensure robustness and generalization.

Machine learning developed a programmed cell death signature for predicting prognosis and immunotherapy benefits in lung adenocarcinoma.

BACKGROUND: Lung cancer is the leading cause of cancer-related deaths worldwide with poor prognosis. Programmed cell death (PCD) plays a crucial function in tumor progression and immunotherapy response in lung adenocarcinoma (LUAD). METHODS: Integrative machine learning procedure including 10 methods was performed to develop a prognostic cell death signature (CDS) using TCGA, GSE30129, GSE31210, GSE37745, GSE42127, GSE50081, GSE68467, GSE68571, and GSE72094 dataset. The correlation between CDS and tumor immune microenvironment was evaluated using various methods and single cell analysis. qRT-PCR and CCK-8 assay were conducted to explore the biological functions of hub gene. RESULTS: The prognostic CDS developed by Lasso + survivalSVM method was regarded as the optimal prognostic model. The CDS had a stable and powerful performance in predicting the clinical outcome of LUAD and served as an independent risk factor in TCGA and 8 GEO datasets. The C-index of CDS was higher than that of clinical stage and many developed signatures for LUAD. LUAD patients with low CDS score had a higher PD1&CTLA4 immunophenoscore, higher TMB score, lower TIDE score and lower tumor escape score, indicating a better immunotherapy benefit. Single cell analysis revealed a strong and frequent communication between epithelial cells and cancer-related fibroblasts by specific ligand-receptor pairs, including COL1A2-SDC4 and COL1A2-SDC1. Vitro experiment showed that SLC7A5 was upregulated in LUAD and knockdown of SLC7A5 obviously suppressed tumor cell proliferation. CONCLUSION: Our study developed a novel CDS for LUAD. The CDS served as an indicator for predicting the prognosis and immunotherapy benefits of LAUD patients.

Exosome-mediated metabolic reprogramming: Implications in esophageal carcinoma progression and tumor microenvironment remodeling.

Esophageal carcinoma is among the most fatal malignancies with increasing incidence globally. Tumor onset and progression can be driven by metabolic reprogramming, especially during esophageal carcinoma development. Exosomes, a subset of extracellular vesicles, display an average size of ∼100 nanometers, containing multifarious components (nucleic acids, proteins, lipids, etc.). An increasing number of studies have shown that exosomes are capable of transferring molecules with biological functions into recipient cells, which play crucial roles in esophageal carcinoma progression and tumor microenvironment that is a highly heterogeneous ecosystem through rewriting the metabolic processes in tumor cells and environmental stromal cells. The review introduces the reprogramming of glucose, lipid, amino acid, mitochondrial metabolism in esophageal carcinoma, and summarize current pharmaceutical agents targeting such aberrant metabolism rewiring. We also comprehensively overview the biogenesis and release of exosomes, and recent advances of exosomal cargoes and functions in esophageal carcinoma and their promising clinical application. Moreover, we discuss how exosomes trigger tumor growth, metastasis, drug resistance, and immunosuppression as well as tumor microenvironment remodeling through focusing on their capacity to transfer materials between cells or between cells and tissues and modulate metabolic reprogramming, thus providing a theoretical reference for the design potential pharmaceutical agents targeting these mechanisms. Altogether, our review attempts to fully understand the significance of exosome-based metabolic rewriting in esophageal carcinoma progression and remodeling of the tumor microenvironment, bringing novel insights into the prevention and treatment of esophageal carcinoma in the future.

Crowd-sourced and expert video assessment in minimally invasive esophagectomy.

BACKGROUND: Video-based assessment by experts may structurally measure surgical performance using procedure-specific competency assessment tools (CATs). A CAT for minimally invasive esophagectomy (MIE-CAT) was developed and validated previously. However, surgeon's time is scarce and video assessment is time-consuming and labor intensive. This study investigated non-procedure-specific assessment of MIE video clips by MIE experts and crowdsourcing, collective surgical performance evaluation by anonymous and untrained laypeople, to assist procedure-specific expert review. METHODS: Two surgical performance scoring frameworks were used to assess eight MIE videos. First, global performance was assessed with the non-procedure-specific Global Operative Assessment of Laparoscopic Skills (GOALS) of 64 procedural phase-based video clips < 10 min. Each clip was assessed by two MIE experts and > 30 crowd workers. Second, the same experts assessed procedure-specific performance with the MIE-CAT of the corresponding full-length video. Reliability and convergent validity of GOALS for MIE were investigated using hypothesis testing with correlations (experience, blood loss, operative time, and MIE-CAT). RESULTS: Less than 75% of hypothesized correlations between GOALS scores and experience of the surgical team (r < 0.3), blood loss (r = - 0.82 to 0.02), operative time (r = - 0.42 to 0.07), and the MIE-CAT scores (r = - 0.04 to 0.76) were met for both crowd workers and experts. Interestingly, experts' GOALS and MIE-CAT scores correlated strongly (r = 0.40 to 0.79), while crowd workers' GOALS and experts' MIE-CAT scores correlations were weak (r = - 0.04 to 0.49). Expert and crowd worker GOALS scores correlated poorly (ICC ≤ 0.42). CONCLUSION: GOALS assessments by crowd workers lacked convergent validity and showed poor reliability. It is likely that MIE is technically too difficult to assess for laypeople. Convergent validity of GOALS assessments by experts could also not be established. GOALS might not be comprehensive enough to assess detailed MIE performance. However, expert's GOALS and MIE-CAT scores strongly correlated indicating video clip (instead of full-length video) assessments could be useful to shorten assessment time.

Validity of Using Pathological Response as a Surrogate for Overall Survival in Neoadjuvant Studies for Esophageal Cancer: A Systematic Review and Meta-analysis.

BACKGROUND: Pathological response is a critical factor in predicting long-term survival of patients with esophageal cancer after preoperative therapy. However, the validity of using pathological response as a surrogate for overall survival (OS) for esophageal cancer has not yet been established. In this study, a literature-based meta-analysis was conducted to evaluate pathological response as a proxy endpoint for survival in esophageal cancer. METHODS: Three databases were systematically searched to identify relevant studies investigating neoadjuvant treatment for esophageal cancer. The correlation between pathological complete response (pCR) and OS were assessed using a weighted multiple regression analysis at the trial level, and the coefficient of determination (R2) was calculated. The research design and histological subtypes were considered in the performance of subgroup analysis. RESULTS: In this meta-analysis, a total of 40 trials, comprising 43 comparisons and 55,344 patients were qualified. The surrogacy between pCR and OS was moderate (R2 = 0.238 in direct comparison, R2 = 0.500 for pCR reciprocals, R2 = 0.541 in log settings). pCR could not serve as an ideal surrogate endpoint in randomized controlled trials (RCTs) (R2 = 0.511 in direct comparison, R2 = 0.460 for pCR reciprocals, R2 = 0.523 in log settings). A strong correlation was observed in studies comparing neoadjuvant chemoradiotherapy and neoadjuvant chemotherapy (R2 = 0.595 in direct comparison, R2 = 0.840 for pCR reciprocals, R2 = 0.800 in log settings). CONCLUSIONS: A lack of surrogacy of pathological response for long-term survival at trial level is established in this study. Hence, caution should be exercised when using pCR as the primary endpoint in neoadjuvant studies for esophageal cancer.

Development and Validation of PET/CT-Based Nomogram for Preoperative Prediction of Lymph Node Status in Esophageal Squamous Cell Carcinoma.

PURPOSE: This study was conducted to predict the lymph node status and survival of esophageal squamous cell carcinoma before treatment by PET-CT-related parameters. METHODS: From January 2013 to July 2018, patients with pathologically diagnosed ESCC at our hospital were retrospectively enrolled. Completed esophagectomy and two- or three-field lymph node dissections were conducted. Those with neoadjuvant therapy were excluded. The first 65% of patients in each year were regarded as the training set and the last 35% as the test set. Nomogram was constructed by the "rms" package. Five-year, overall survival was analyzed based on the best cutoff value of risk score determined by the "survivalROC" package. RESULTS: Ultimately, 311 patients were included with 209 in the training set and 102 in the test set. The positive rate of the lymph node in the training set was 36.8% and that in the test set was 32.4%. The C-index of the training set was 0.763 and the test set was 0.766. The decision curve analysis showed that it was superior to the previous methods based on lymph node uptake or long/short axis diameter or axial ratio. Risk score > 0.20 was significantly associated with 5-year, overall survival (p = 0.0015) in all patients. CONCLUSIONS: The nomogram constructed from PET-CT parameters including primary tumor metabolic length and thickness can accurately predict the risk of lymph node metastasis in ESCC. The risk score calculated by our model accurately predicts the patient's 5-year overall survival.

Comparison of neoadjuvant nab-paclitaxel plus immunotherapy versus paclitaxel plus immunotherapy for esophageal squamous cell carcinoma.

BACKGROUND: This study aimed to compare the feasibility of nab-paclitaxel plus platinum-based chemotherapy (nabTP) versus paclitaxel plus platinum-based chemotherapy (TP) with immune checkpoint inhibitors (ICIs) as a neoadjuvant modality for locally resectable esophageal squamous cell carcinoma (ESCC). METHODS: Between April 2019 and March 2022, we identified ESCC patients who received neoadjuvant immunotherapy with both nabTP (n = 213) and TP (n = 98) at our institution and Henan Cancer Hospital. The patients in the ICIs-nabTP and ICIs-TP groups were pair-matched (1:1) for tumor location, sex, smoking, drinking, clinical T and N stage. The primary endpoint was the hazard of 30-day major postoperative complications. Second, logistic models were applied to estimate the risk factors for pathological complete response (pCR) rate. RESULTS: All patients underwent esophagectomy with R0 resection. A statistically significant increase in the risk of developing major pulmonary (odds ratio [OR], 1.182; 95% confidence interval [CI]: 0.530-2.635; p = 0.683), anastomotic (OR, 1.881; 95% CI: 0.607-5.830; p = 0.267), cardiac (OR, 1.000; 95% CI: 0.426-2.349; p = 1.000) complications after neoadjuvant immunotherapy plus nabTP was not observed. The median interval to surgery was 39 days in the ICIs-nabTP group versus 44 days in the ICIs-TP group (p = 0.119). There was no 30-day mortality in each group. However, there was a slight difference in the 30-day readmission rate (p = 0.043) and the incidence of hydropneumothorax (p = 0.027) between the two groups. The pCR rates of the ICIs-nabTP and ICIs-TP group were 36.7 and 21.4%, respectively (p = 0.018). CONCLUSIONS: It appears to be feasible to add immunotherapy to nabTP regimen for locally advanced ESCC. Compared with TP, nabTP plus ICIs can achieve a better pCR rate in ESCC.

Mechanisms and characteristics of subcapsular sinus macrophages in tumor immunity: a narrative review.

Background and Objective: Lymph nodes constitute an integral component of the secondary lymphoid organs, housing a diverse population of macrophages. Macrophages exhibit heterogeneity in terms of localization, phenotype and ontogeny. Recent evidence has established that subcapsular sinus macrophages (SCSMs) are the initial cells exposed to antigens from afferent lymph vessels, playing a crucial role in the host immune response against invading pathogens and tumor cells. In order to summarize the role and mechanisms of SCSM in tumor immunity, this study systematically reviews research on SCSMs in tumor immunity. Methods: A systematic search was conducted in PubMed and Web of Science to identify articles investigating clinical significance and mechanisms of SCSMs. Study eligibility was independently evaluated by two authors based on the assessment of titles, abstracts and full-texts. Key Content and Findings: The narrative review included a total of 17 studies. Previous research consistently showed that a high level of SCSM in patients with various carcinomas is associated with a favorable long-term prognosis. SCSM acts as the front-line defender in antitumor activity, engaging in intricate communication with other immune cells. Moreover, SCSM could directly and indirectly modulate tumor immunity, and the integrity of SCSM layer is interrupted in disease status. Several studies explored the feasibility of targeting SCSM to activate immunity against tumors. However, the direct molecular interactions and alternation in signal pathway in the tumor immunity of SCSM are less well established in previous researches. Conclusions: This narrative review underscores the critical role of SCSM in tumor immunity. Future studies should focus on the deeper mechanism underlying SCSMs and explore their clinical applications.

Whole-process nursing management for laparo-gastroscopic esophagectomy.

Background: Advances in surgical, anesthesia, and nursing techniques have allowed the development of laparo-gastroscopic esophagectomy (LGE) as a minimally invasive treatment of esophageal cancer. This study summarizes the experience of patient whole-process nursing management for patients who received LGE. Methods: The implementation of LGE at Zhongshan Hospital, Fudan University, was initiated in June 2020. The procedure is indicated for patients with thoracic conditions that can compromise the outcomes of traditional surgical procedures, and is performed coordinately by thoracic surgeons and endoscopists. A whole-process nursing protocol covering peri-operative patient management was proposed based on the LGE procedure. The operative outcomes were analyzed in this study. Results: The data of 10 consecutive patients who received LGE and the whole-process nursing protocol were analyzed, and all patients were compliant with the nursing protocol. Intra-operatively, there were no complications or conversions to other surgical methods. Post-operatively, pulmonary complications occurred in 2 cases [1 patient experienced aspiration, underwent preventive tracheotomy, and was discharged on postoperative day (POD) 10; 1 patient developed a left pleural effusion requiring puncture and drainage, and was discharged on POD 7]. The 30-day mortality was not recorded from the primary LGE cohort. Conclusions: The whole-process nursing protocol showed safety and feasibility for patients who underwent LGE. In the future, more specialized and whole-process nursing management will be carried out for patients undergoing such operations.

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.

CircBCAR3 accelerates esophageal cancer tumorigenesis and metastasis via sponging miR-27a-3p.

RATIONALE: Circular RNAs (circRNAs) have been demonstrated to contribute to esophageal cancer progression. CircBCAR3 (hsa_circ_0007624) is predicted to be differentially expressed in esophageal cancer by bioinformatics analysis. We investigated the oncogenic roles and biogenesis of circBCAR3 in esophageal carcinogenesis. METHODS: Functions of circBCAR3 on cancer cell proliferation, migration, invasion, and ferroptosis were explored using the loss-of-function assays. A xenograft mouse model was used to reveal effects of circBCAR3 on xenograft growth and lung metastasis. The upstream and downstream mechanisms of circBCAR3 were investigated by bioinformatics analysis and confirmed by RNA immunoprecipitation and luciferase reporter assays. The dysregulated genes in hypoxia-induced esophageal cancer cells were identified using RNA-seq. RESULTS: CircBCAR3 was highly expressed in esophageal cancer tissues and cells and its expression was increased by hypoxia in vitro. Silencing of circBCAR3 repressed the proliferation, migration, invasion, and ferroptosis of esophageal cancer cells in vitro, as well as inhibited the growth and metastasis of esophageal xenograft in mice in vivo. The hypoxia-induced promotive effects on esophageal cancer cell migration and ferroptosis were rescued by circBCAR3 knockdown. Mechanistically, circBCAR3 can interact with miR-27a-3p by the competitive endogenous RNA mechanism to upregulate transportin-1 (TNPO1). Furthermore, our investigation indicated that splicing factor quaking (QKI) is a positive regulator of circBCAR3 via targeting the introns flanking the hsa_circ_0007624-formed exons in BCAR3 pre-mRNA. Hypoxia upregulates E2F7 to transcriptionally activate QKI. CONCLUSION: Our research demonstrated that splicing factor QKI promotes circBCAR3 biogenesis, which accelerates esophageal cancer tumorigenesis via binding with miR-27a-3p to upregulate TNPO1. These data suggested circBCAR3 as a potential target in the treatment of esophageal cancer. Hypoxia induces the upregulation of E2F7, which transcriptionally activates QKI in esophageal cancer cells. QKI increases the formation of circBCAR3 by juxtaposing the circularized exons. CircBCAR3 binds with miR-27a-3p to promote TNPO1 expression. CircBCAR3 promoted the proliferation, migration, invasion, and ferroptosis of esophageal cancer cells by miR-27a-3p.

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.

External validation of the eighth edition of the TNM classification for lung cancer in small cell lung cancer.

OBJECTIVES: The newly released eighth edition of the American Joint Committee on Cancer TNM staging system for lung cancer seeks to improve prognostic accuracy but lacks external validation for small cell lung cancer (SCLC). Moreover, previous studies posed a few questions concerning survival differences for patients with specific site N3 node involvement or single-site metastasis (SSM) in different distant organs. The aim of this study was to validate the eighth edition of the TNM classification for SCLC in an independent multi-institutional cohort from China and answer the questions raised by the previous research. METHODS: Patients with SCLC from four Chinese cancer centers between 2009 and 2019 were reclassified according to the seventh and eighth edition of the TNM classification. Survival was estimated using the Kaplan-Meier method. Comparisons between adjacent categories and stage groups were performed using Cox proportional hazard regression. R2 statistics were calculated to evaluate the discriminating performance of editions. RESULTS: Of 3384 enrolled cases, 3358 had clinical stage, 537 had pathological stage, and 511 had both. Progressive deterioration of survival was observed with advancing of TNM categories and stages both in the seventh and the eighth edition. The eighth edition stages had a higher R2 statistic than the seventh edition (0.207 versus 0.197). Newly defined categories M1b and M1c and stages IIIC, IVA and IVB in the eighth edition discriminated groups with significantly different prognosis. Patients with N3 contralateral supraclavicular nodes had a significantly worse prognosis than those without (p = 0.032). For patients with single-site metastasis, liver involvement showed a worse prognosis compared to brain involvement (p = 0.030). CONCLUSIONS: Our study provided an external validation of the eighth edition of the TNM classification for lung cancer in Chinese patients with SCLC, and confirmed its improved prognostic accuracy compared with the seventh edition. Patients with N3 and M1b might represent heterogeneous populations that warrant further research.

Transcervical versus transthoracic minimally invasive esophagectomy: a randomized and controlled trial protocol.

Background: Anatomically, the esophagus is located within the mediastinum, and thus it potentially a transcervical approach for esophagectomy, which avoids thoracic manipulation, could be an alternative to transthoracic esophagectomy for the surgical resection of esophageal cancer. A modified transcervical minimally invasive esophagectomy (MIE), laparo-gastroscopic esophagectomy (LGE), was recently introduced using an integrated gastroscope to mobilize the esophagus. As such, a randomized controlled trial (RCT) is necessary to validate its value compared to transthoracic MIE, which carries a high risk of morbidity due to thoracic manipulation. Methods: This prospective study plans to enroll patients with resectable esophageal cancer with a pathological diagnosis of squamous cell carcinoma or adenocarcinoma patients over a 2-year period. Patients will be randomly assigned to one of 2 groups in a 1:1 ratio: patients in Group A will radical LGE and patients in Group B will receive radical laparo-thoracoscopic esophagectomy (LTE). Perioperative and long-term outcomes of all patients will be collected and analyzed. The primary end point will be perioperative morbidity, and the secondary end points will include 5-year overall survival (OS) and disease-free survival (DFS) and quality of life (QOL) score. Other data that will be collected and compared between the groups include the number of harvested lymph nodes, surgical Apgar score, and duration of operation. Discussion: Transthoracic MIE is the most widely accepted approach for treating esophageal cancer. In this RCT, transthoracic MIE and transcervical LGE will be compared with respect to oncological and surgical outcomes (oncological none-inferiority and surgical superiority). Trial Registration: This study is registered in Chinese Clinical Trial Registry (ChiCTR2200055312) with the name of 'Transcervical versus Transthoracic Minimally Invasive Esophagectomy: A Randomized and Controlled Trial' on January 6, 2022. Details can be found on http://www.chictr.org.cn/showproj.aspx?proj=133224.

Treatment of anastomotic leak after esophagectomy: insights of an international case vignette survey and expert discussions.

Anastomotic leak (AL) is a severe complication after esophagectomy. Clinical presentation of AL is diverse and there is large practice variation regarding treatment of AL. This study aimed to explore different AL treatment strategies and their underlying rationale. This mixed-methods study consisted of an international survey among upper gastro-intestinal (GI) surgeons and focus groups with expert upper GI surgeons. The survey included 10 case vignettes and data sources were integrated after separate analysis. The survey was completed by 188 respondents (completion rate 69%) and 6 focus groups were conducted with 20 international experts. Prevention of mortality was the most important goal of primary treatment. Goals of secondary treatment were to promote tissue healing, return to oral feeding and safe hospital discharge. There was substantial variation in the preferred treatment principles (e.g. drainage or defect closure) and modalities (e.g. stent or endoVAC) within different presentations of AL. Patients with local symptoms were treated by supportive means only or by non-surgical drainage and/or defect closure. Drainage was routinely performed in patients with intrathoracic collections and often combined with defect closure. Patients with conduit necrosis were predominantly treated by resection and reconstruction of the anastomosis or by esophageal diversion. This mixed-methods study shows that overall treatment strategies for AL are determined by vitality of the conduit and presence of intrathoracic collections. There is large variation in preferred treatment principles and modalities. Future research may investigate optimal treatment for specific AL presentations and aim to develop consensus-based treatment guidelines for AL after esophagectomy.

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.

Advancing Gastroscope From Intraluminal to Extraluminal Dissection: Primary Experience of Laparo-gastroscopic Esophagectomy.

Transhiatal esophagectomy facilitates esophageal resection without the need for thoracotomy. However, this procedure carries the risks of blind and blunt dissection within the mediastinum. More recently, video-assisted or mediastinoscopic transhiatal esophagectomy was introduced to mobilize the esophagus under direct visualization. Even though, the procedure is technically demanding and animal studies have shown that the CO2 pneumomediastinum may be associated with hemodynamic instability. By further developing already established techniques, we pioneered the transhiatal esophageal mobilization by using hybrid gastroscope (Fig. 1). Laparo-gastroscopic esophagectomy, which integrates gastroscope and laparoscope for esophageal mobilization, was successfully implemented on an esophageal cancer patient with a history of lung cancer surgery. The operative duration was 240 minutes with an estimated blood loss of 110 mL. The patient experienced an uneventful recovery and was discharged on postoperative day 9. Further studies will be required to confirm the surgical and oncological efficacy of this innovation.