Background: The NALLC trial (NCT01441752) demonstrated that postoperative adjuvant chemotherapy combined with traditional Chinese medicine (TCM) improved the quality of life (QoL) and survival in resected stage Ib-IIIa non-small-cell lung cancer (NSCLC) patients. This report updates disease-free survival (DFS) and other key outcomes.Methods: Between December 2012 and August 2015, 334 patients were randomized to receive either adjuvant chemotherapy plus traditional Chinese herbal granules (n = 167) or adjuvant chemotherapy plus placebo (n = 167) across 7 centers. Patients continued herbal granules or placebo daily until chemotherapy completion. DFS updates data was conducted in the intention-to-treat (ITT) population.Results: The median follow-up was 116.87 months. Median DFS was 71.83 months for the TCM group versus 43.60 months for the control (HR: .86; 95% CI: .64-1.15; P = .31). Two-year and 5-year DFS rates were 73.60% and 50.16% for TCM, compared to 67.45% and 44.08% for the control (P = .23). Median overall survival (mOS) was not reached in either group, with 75% OS at 63.40 months for TCM and 53.67 months for the control. Five-year OS rates were 76.15% for TCM and 69.81% for the control (P = .23). Subgroup analysis showed stage Ib patients benefited from TCM in both DFS (HR: .51; P = .02) and OS (HR: .34; P = .01).Conclusions: Adjuvant chemotherapy combined with TCM showed a potential trend toward improved DFS in early-stage NSCLC patients.Trial registration: This trial was registered with Clinical.Trials.gov (Number: NCT01441752, July 14, 2011).

To prove the concept of conversion surgery after induction therapy in initially unresectable stage III non-small-cell lung cancer (NSCLC), we conducted this single-arm, open label, prospective study. In this proof-of-concept prospective study, patients with initially unresectable stage III NSCLC who had received induction therapy and evaluated radically resectable were included and underwent surgery. The primary outcome was perioperative morbidity. Bulk-RNA sequencing of baseline and post-treatment samples from patients receiving immunochemotherapy (ICT) as induction therapy was conducted to explore the transcriptomic characteristics of therapeutic response. This study was registered with ClinicalTrials.gov, NCT04945928. From August 2021 to January 2024, 30 patients were enrolled. The R0 resection rate was 93.3

Background:Previous studies have demonstrated that ultrasonic energy devices are safe and effective for sealing blood vessels in thoracoscopic surgery. However, no randomized controlled trials have been conducted to evaluate the safety and efficacy of using ultrasonic energy devices to seal blood vessels measuring 5-7 mm. This study aimed to compare the success rate of sealing 5-7 mm blood vessels between the SOUND REACH SR7 Shears (SRB) and the HARMONIC ACE +7 Shears with Advanced Hemostasis (ACE+7). Methods:In this multicenter, noninferiority, randomized controlled trial, patients at four hospitals in China scheduled for thoracoscopic surgery with at least one blood vessel requiring sealing, as indicated by preoperative computed tomography (CT) images, were randomly assigned in a 1:1 ratio to either the SRB group or the ACE+7 group. The primary endpoint was the success rate of sealing target blood vessels. Results:A total of 144 patients were enrolled between August and December 2023, and 133 patients were included in the full analysis set (FAS): 67 (50.4%) in the SRB group and 66 (49.6%) in the ACE+7 group. The SRB group included 37 lobectomies and 30 segmentectomies, while the ACE+7 group included 34 lobectomies, 30 segmentectomies, and two esophagectomies. A total of 67 blood vessels (62 arteries and five veins) were sealed in the SRB group, and 66 blood vessels (61 arteries and five veins) were sealed in the ACE+7 group. The success rate of sealing was 100% in both groups with an absolute difference of 0% (95% confidence interval: -5.5% to 5.4%) that did not cross the prespecified noninferiority margin of -10%. Conclusions:SRB demonstrated a non-inferior success rate for sealing 5-7 mm blood vessels in thoracoscopic surgery. SRB could be considered an alternative to ACE+7 for sealing 5-7 mm blood vessels in thoracoscopic surgery. Trial Registration:This study was registered at ClinicalTrials.gov (NCT06002737).

The role of preoperative anti-PD-1 antibody (pembrolizumab) plus chemoradiotherapy (PPCT) in locally advanced, resectable esophageal squamous cell carcinoma (ESCC) is still unclear. We aimed to investigate the therapeutic effect and safety of PPCT followed by surgery in this study (NCT03792347, NCT04435197). Patients with histologically confirmed, locally advanced, and surgically resectable ESCC were enrolled. They received PPCT with paclitaxel/carboplatin or nab-paclitaxel/carboplatin, followed by esophagectomy 4-6 weeks after treatment. The primary endpoint was the pathologic complete response (pCR) rate. Tumor specimens, blood samples and subcutaneous tumor mouse models were utilized to explore and validate the dynamic characteristics of the tumor microenvironment (TME) of ESCC after PPCT. Among the 143 patients enrolled, 140 received neoadjuvant treatment, and 125 underwent surgery. The pCR rate reached 43.2% (54/125). During neoadjuvant period, 75.7% (106/140) of patients experienced grade three or higher-grade adverse events. After a median follow-up of 17.4 months, patients showed a one-year disease-free survival rate of 91.1%, and an overall survival rate of 96.5%. Using scRNA-seq and cytokine profiling, we identified high IL-6 levels as a predictor of response to PPCT. In vivo experiment revealed that IL-6 neutralization enhanced the efficacy of immunotherapy by increasing CD4+ T-cell cytotoxicity. This is the first large-scale, multicenter, phase 1/2 trial reporting the short-term results of PPCT for locally advanced resectable ESCC. Although the short-term efficacy was not superior to that of neoadjuvant chemoradiotherapy, PPCT demonstrated acceptable safety and comparable one-year survival. We also revealed an association between the therapeutic response and the ability of anti-IL-6 blockade to enhance the efficacy of immunotherapy.

Background The long-term survival and perioperative outcomes of robotic-assisted lobectomy (RAL) and video- assisted lobectomy (VAL) in resectable non-small-cell lung cancer (NSCLC) were found to be comparable in retrospective studies, but they have not been investigated in a randomized trial setting. We conducted the RVlob trial to investigate if RAL was non-inferior to VAL in patients with resectable NSCLC. Methods In this single-center, open-label, and parallel-arm randomized controlled trial conducted in Ruijin Hospital (Shanghai, China) between May 2017 and May 2020, we randomly assigned patients with resectable NSCLC in a 1:1 ratio to receive either RAL or VAL. One of the primary endpoints was 3-year overall survival. Secondary endpoints included 3-year disease-free survival. The Kaplan-Meier - Meier approach was used to calculate overall survival and disease-free survival at 3 years. This study was registered with ClinicalTrials.gov, NCT03134534. Findings A total of 320 patients were randomized to receive RAL (n = 157) or VAL (n = 163). The baseline characteristics of patients were well balanced between the two groups. After a median follow-up of 58.0 months, the 3-year overall survival was 94.6% (95% confidence fi dence interval [CI], 91.0-98.3) - 98.3) in the RAL group and 91.5% (95% CI, 87.2-96.0) - 96.0) in the VAL group (hazard ratio [HR] for death, 0.65; 95% CI, 0.33-1.28; - 1.28; P = 0.21); noninferiority of RAL was confirmed fi rmed according to the predefined fi ned margin of - 5% (absolute difference, 2.96%; a one-sided 90% CI, - 1.39% to infinity ; P = 0.0029 for noninferiority). The 3-year disease-free survival was 88.7% (95% CI, 83.6-94.1) - 94.1) in the RAL group and 85.4% (95% CI, 80.0-91.2) - 91.2) in the VAL group (HR for disease recurrence or death, 0.87; 95% CI, 0.50-1.52; - 1.52; P = 0.62). Interpretation This study is the fi rst randomized trial to show that RAL resulted in non-inferior overall survival compared with VAL in patients with resectable NSCLC. Based on our results, RAL is an equally oncologically effective treatment and can be considered as an alternative to VAL for resectable NSCLC. Funding National Natural Science Foundation of China (82072557), National Key Research and Development Program of China (2021YFC2500900), Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant (20172005, the 2nd round of disbursement), program of Shanghai Academic Research Leader from Science and Technology Commission of Shanghai Municipality (20XD1402300), Novel Interdisciplinary Research Project from Shanghai Municipal Health Commission (2022JC023), and Interdisciplinary Program of Shanghai Jiao Tong University (YG2023ZD04). Copyright (c) 2024 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

BACKGROUND:Dynamic alterations of the tumor immune microenvironment in esophageal squamous cell carcinoma (ESCC) after different neoadjuvant therapies were understudied.METHODS:We used mass cytometry with a 42-antibody panel for 6 adjacent normal esophageal mucosa and 26 tumor samples (treatment-naïve, n=12; postneoadjuvant, n=14) from patients with ESCC. Single-cell RNA sequencing of previous studies and bulk RNA sequencing from The Cancer Genome Atlas were analyzed, flow cytometry, immunohistochemistry, and immunofluorescence analyses were performed.RESULTS:Poor tumor regression was observed in the neoadjuvant chemotherapy group. Radiotherapy-based regimens enhanced CD8+ T cells but diminished regulatory T cells and promoted the ratio of effector memory to central memory T cells. Immune checkpoint blockade augmented NK cell activation and cytotoxicity by increasing the frequency of CD16+ NK cells. We discovered a novel CCR4+CCR6+ macrophage subset that correlated with the enrichment of corresponding chemokines (CCL3/CCL5/CCL17/CCL20/CCL22). We established a CCR4/CCR6 chemokine-based model that stratified ESCC patients with differential overall survival and responsiveness to neoadjuvant chemoradiotherapy combined with immunotherapy, which was validated in two independent cohorts of esophageal cancer with neoadjuvant treatment.CONCLUSIONS:This work reveals that neoadjuvant therapy significantly regulates the cellular composition of the tumor immune microenvironment in ESCC and proposes a potential model of CCR4/CCR6 system to predict the benefits from neoadjuvant chemoradiotherapy combined with immunotherapy.

Objective: To determine whether RAL affects perioperative outcomes and long-term efficacy in NSCLC patients, compared with traditional VAL. Summary of Background Data: RAL is a promising treatment for NSCLC. However, its efficacy has not been fully evaluated. Methods: A single-center, open-labeled prospective randomized clinical trial was launched in May 2017 to compare the efficacy of RAL and VAL. By May 2020, 320 patients were enrolled. The perioperative results of RAL and VAL were compared. Results: The 320 enrolled patients were randomly assigned to the RAL group (n = 157) and the VAL group (n = 163). Perioperative outcomes were comparable between the 2 groups, including the length of hospital stay ( P = 0.76) and the rate of postoperative complications ( P = 0.45). No perioperative mortality occurred in either group. The total amount of chest tube drainage {830 mL [interquartile range (IQR), 550–1130 mL] vs 685 mL [IQR, 367.5–1160 mL], P = 0.007} and hospitalization costs [$12821 (IQR, $12145–$13924) vs $8009 (IQR, $7014–$9003), P < 0.001] were significantly higher in the RAL group. RAL group had a significantly higher number of LNs harvested [11 (IQR, 8–15) vs 10 (IQR, 8–13), P = 0.02], higher number of N1 LNs [6 (IQR, 4–8) vs 5 (IQR, 3–7), P = 0.005], and more LN stations examined [6 (IQR, 5–7) vs 5 (IQR, 4–6), P < 0.001]. Conclusions: Both RAL and VAL are safe and feasible for the treatment of NSCLC. RAL achieved similar perioperative outcomes, together with higher LN yield. Further follow-up investigations are required to evaluate the long-term efficacy of RAL. (ClinicalTrials.gov identifier: NCT03134534)

单孔胸腔镜手术是肺癌微创治疗的重要方式.2010年,单孔胸腔镜手术首次应用于肺癌治疗;2019年、2020年,欧洲共识和中国共识相继发表.最新发表的中国共识分别从单孔胸腔镜手术的定义、用于肺癌治疗的适应证、安全性及可行性、手术技巧、学习曲线、短期及长期结果等方面为单孔胸腔镜手术标准化提供建议,对提高手术质量及减少相关并发症的发生至关重要.中国共识也对剑突下单孔胸腔镜、不插管麻醉单孔胸腔镜的现状进行了讨论,考虑到两者的技术难度与挑战性,其在临床治疗中的应用仍有一定限制.本文旨在对中国共识进行解读并比较其与欧洲共识的异同,为广大胸外科同仁提供参考.

BACKGROUND:Autophagy has a dual function in cancer, and its role in carcinogenesis of the esophagus remains poorly understood. In the present study, we explored the prognostic value of autophagy in esophageal cancer (ESCA), one of the leading causes of cancer-related deaths worldwide.METHODS:Using ESCA RNA-sequencing (RNA-Seq) data from 158 primary patients with ESCA, including esophageal adenocarcinoma and esophageal squamous cell carcinoma, were downloaded from The Cancer Genome Atlas (TCGA) for this study. We obtained differentially expressed autophagy-related genes (ARGs) by the "limma" package of R. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genome (KEGG) analyses unveiled several fundamental signaling pathways associated with the differentially expressed ARGs in ESCA. Univariate Cox regression analyses were used to estimate associations between ARGs and overall survival (OS) in the TCGA ESCA cohort. A Cox proportional hazards model (iteration =1,000) with a lasso penalty was used to create the optimal multiple-gene prognostic signature utilizing an R package called "glmnet".RESULTS:A prognostic signature was constructed with four ARGs (DNAJB1, BNIP1, VAMP7 and TBK1) in the training set, which significantly divided ESCA patients into high- and low-risk groups in terms of OS [hazard ratio (HR) =1.508, 95% confidence interval (CI): 1.201-1.894, P<0.001]. In the testing set, the risk score remained an independent prognostic factor in the multivariate analyses (HR =1.572, 95% CI: 1.096-2.257, P=0.014). The area under the curve (AUC) of the receiver operating characteristic (ROC) predicting 1-year survival showed a better predictive power for the prediction model. The AUC in training and testing cohorts were 0.746 and 0.691, respectively. Therefore, the prognostic signature of the four ARGs was successfully validated in the independent cohort.CONCLUSIONS:The prognostic signature may be an independent predictor of survival for ESCA patients. The prognostic nomogram may improve the prediction of individualized outcome. This study also highlights the importance of autophagy in the outcomes of patients with ESCA.

The effects of autophagy and apoptosis in the prognostic assessment and treatment of Esophageal squamous cell carcinoma (ESCC) remain to be elucidated. Here, we conducted a retrospective study on the histopathology of ESCC, investigated the expression of Beclin-1 and Bcl-2 proteins (both autophagy- and apoptosis-related) in esophageal cancer tissue, and analyzed the significance of these proteins for the prognosis of ESCC. In the present study, the expression level of Beclin-1 in ESCC was significantly lower than that in adjacent tissues (p < 0.01), whereas the expression level of Bcl-2 showed the opposite pattern (p < 0.01). Furthermore, low expression of Beclin-1 was associated with more advanced ESCC stages and lymph node metastasis. However, high expression of Bcl-2 was associated with more advanced ESCC stages, deeper tumor invasion, and lymph node metastasis. Moreover, the relationship between Bcl-2 expression and OS was not significant (p > 0.05), whereas Beclin-1 expression was significantly associated with OS (p < 0.05). Subgroup analysis showed that Beclin-1 expression was significantly associated with OS in the high-Bcl-2-expression group but not in the low-Bcl-2-expression group. Importantly, Beclin-1 upregulation or downregulation significantly upregulated or downregulated invasion, respectively, in EC9706 cells in combination with high expression but not low expression of Bcl-2. These findings reveal that differences in autophagy and apoptotic states and their activities may promote malignant tumor differentiation, which could lead to a more aggressive esophageal squamous cell phenotype and a worse survival prognosis. Here, Beclin-1 was shown to be a promising prognostic biomarker and therapeutic target for patients with ESCC in the high-Bcl-2-expression population.

Objective. The question of whether the tumor mutation burden (TMB) is associated with either improved survival outcomes or improvement of immunotherapies remains controversial in various malignancies. The aim of this study is to investigate the genomic landscape of the relationship between TMB and immune cell infiltration in thymic epithelial tumors (TETs). Methods. We downloaded somatic mutation data, transcriptome sequencing data, and clinical information of TETs from the Cancer Genome Atlas (TCGA) database. We assessed the abundance of 22 immune fractions between low-TMB (TMB-L) and high-TMB (TMB-H) groups using the "CIBERSORT" package. Results. Missense mutation had the highest frequency of mutation among the nine variant classifications in TETs. Higher TMB levels were associated with poor survival outcomes (P<0.05), and higher Masaoka stages (P<0.05). More importantly, TMB levels were much higher in the thymic cancer than in thymoma (P<0.01). The infiltration levers of naive CD4(+) T cells and regulatory T cells were significantly higher in the TMB-L group than in the TMB-H group, and this was further associated with better overall survival (OS) in patients with TETs. Conclusion. The present study indicates that the prognosis of TMB-H patients with TETs is significantly poorer than is that of TMB-L patients, which might result from the different levels of infiltration of naive CD4(+) T cells and regulatory T cells.

Thymic epithelial tumors (TET) including thymomas and thymic carcinomas are rare, but they are common primary tumors in the anterior mediastinum. The etiology and tumorigenesis of TET remain unclear. To better understand the novel aberrations of this rare tumor and provide more significant mutation sites for targeted therapy, we performed next-generation sequencing detection on 55 patients with TET. Our results showed that most genes in 12 core pathways harbored aberrations of indeterminate potential. In 4 genes (ARID1A, KMT2C, TGFBR2 and MAP3K1), the indel frequency was above 90%. Dozens of genes, including TGFBR2, KMT2C, PRKDC, ATR, CHD2, SDHA, KDM5A, CHEK1, MSH6 and POLE, possessed frameshift indel with different frequencies in different hotspot sites, which could be the new targets of therapy for TET. For the first time, we revealed a strong correlation between the tumor mutational burden and single nucleotide variations, but not frameshift, on DNA mismatch repair gene MSH6 in TET.

Both robot-assisted Ivor Lewis esophagectomy (RAILE) and conventional thoracoscopic-assisted Ivor Lewis esophagectomy (TAILE) are minimally invasive surgical techniques for the treatment of middle and distal esophageal cancer. However, no research studies comparing early outcomes between RAILE and TAILE have been reported.

BACKGROUND:Anastomosis leakage after esophagectomy is a major threat which leads to many subsequent complications even mortality. But current diagnosis and treatment methods are inefficient. This retrospective study aims to evaluate the utilization of endoscope-assisted mediastinal drainage therapy in treatment for anastomosis leakage after esophagectomy.METHODS:Between January 2014 and June 2018, 51 patients were confirmed anastomosis leakage using gastroscopy. Of them, 23 patients were treated with endoscope-assisted mediastinal drainage therapy (drainage group); and the other 28 patients received endoscope-assisted biomedical fibrin glue occlusion (occlusion group). Short-term clinical outcomes were examined. Factors related to length of postoperative hospitalization (LPH) was analyzed.RESULTS:Endoscope provided highly accurate information on the condition of anastomosis leakage. And there was no evidence that early endoscopy could cause damage to the anastomosis or gastric conduit. One patient from drainage group and two from occlusion group discharged against medical advice. Other 48 patients were completely cured without reoperation or mortality. The median LPH was 32 days in drainage group (range from 17 to 80 days) and 81 days in occlusion group (range from 32 to 190 days), respectively (P<0.05). Linear regression indicated statistically significant correlation between LPH and length from diagnosis to drainage or occlusion (R=0.688, P<0.001).CONCLUSIONS:Endoscope-assisted mediastinal drainage therapy is a satisfactory treatment for anastomosis leakage. Early diagnosis and treatment may facilitate the recovery of anastomosis leakage and reduce LPH.

PURPOSE:To investigate the correlation between the status of epithelial-mesenchymal transition (EMT) of circulating tumor cells (CTCs) and esophageal squamous cell carcinoma (ESCC).METHODS:The demographic data and blood samples of 21 patients with ESCC were collected retrospectively. CTCs were enriched by using optimized CanPatrolTM CTC enrichment technique. CTCs were identified and characterized according to the EMT markers (e-CTCs: epithelial CTCs; mix-CTCs: epithelial-mesenchymal-mixed CTCs; m-CTCs: mesenchymal CTCs). The correlation between CTCs and demographic data was analyzed.RESULTS:Total 129 CTCs were detected in all the patients: 11(8.5%) CTCs of them were e-CTCs, 76(58.9%) were mix-CTCs, and 42(32.6%) were m-CTCs. The average number of CTCs from each patient was 6.1 ± 7.1 which included 0.5 ± 0.9 of e-CTCs, 3.6 ± 5.2 of mix-CTCs, and 2.0 ± 2.7 of m-CTCs; the difference between the three groups was significant (P = 0.017): the number of total CTCs was correlated with the number of mix-CTCs (R2 = 0.883, P < 0.01) and m-CTCs (R2 = 0.639, P < 0.01) but not e-CTCs (R2 = 0.012, P = 0.641) and the number of CTCs was correlated with the N stage and TNM stage in this study (R2 = 0.698 and R2 = 0.359).CONCLUSIONS:Mix-CTCs and m-CTCs might play an important role in progression of ESCC; the number of CTCs in ESCC might have the potential to be a predictor of prognosis.

目的:研究T1期浸润性肺腺癌5种常见病理亚型的临床病理特征及其对预后的影响,为肺腺癌临床监测及治疗提供参考.方法:纳入上海交通大学医学院附属瑞金医院2009年1月至2011年1月间行肺癌手术,且术后经病理检查证实为浸润性肺腺癌、肿瘤直径≤3 cm的患者,分别选取贴壁状为主型、腺泡为主型、乳头状为主型、微乳头状为主型、实性为主型各24例,5组共计120例.对患者的临床病理资料包括年龄、性别、癌胚抗原(carcinoembryonic antigen,CEA)水平、肿瘤分化程度、病理亚型等进行回顾性分析,应用Kaplan-Meier法计算生存率,LogRank检验比较生存差异;多因素COX回归分析判定预后的危险因素.结果:5组不同病理亚型肺腺癌患者的年龄、性别、癌胚抗原(carcinoembryonic antigen,CEA)水平、肿瘤细胞分化程度差异均无统计学意义(P＞0.05),而5组间的胸膜浸润、有无淋巴结转移、术后TNM分期及术后有无复发进展情况差异有统计学意义(P＜0.05).5种肺腺癌亚型中,微乳头状为主型的淋巴结转移率(62.5％)和术后复发转移率(41.6％)最高.进一步行生存率分析显示,贴壁状为主型患者的预后最好,5年生存率为96.0％,微乳头状为主型患者预后最差,5年生存率为66.7％,2组间差异有统计学意义(P＜0.05).病理亚型、淋巴结转移情况、术后TNM分期是影响T1期浸润性肺腺癌患者预后的危险因素,且病理亚型、淋巴结转移情况还是影响其预后的独立危险因素(OR均＞1).结论:T1期浸润性肺腺癌患者的预后与其病理亚型有关,而其中微乳头状为主亚型患者有着较高的淋巴转移率和更差的预后,对于该亚型的T1期浸润性肺腺癌患者,在术后可能需采取更积极的治疗和严密观察.

: The rarity and non-specific symptoms of benign primary tracheal tumors always leaded to misdiagnosis and delayed treatment, and also undefined the optimal treatment. In this case, a 45-year-old woman had a history of progressive shortness of breath and dry cough for several years, CT scan revealed an intra-luminal tracheal mass invaded the left side of tracheal wall. After being located by bronchoscope preoperatively, the tumor was removed by surgical resection. The tumor was 1.5 cm in diameter with intact capsule. The pathological result confirmed the diagnosis of schwannoma.