4091 Background: Adenocarcinoma of the esophagogastric junction (AEG) is a malignant tumor with high morbidity and mortality globally. Among subtypes, Siewert type Ⅱ AEG remains a clinical challenge owing to its unique anatomical location and distinct clinicopathological features. This study aimed to evaluate the efficacy and safety of Tislelizumab in combination with oxaliplatin and S-1 as neoadjuvant therapy for patients with locally advanced Siewert type Ⅱ AEG. Methods: This is a prospective, multicenter clinical trial. Eligible patients were aged 19-75 years with pathologically confirmed Siewert type II adenocarcinoma of the esophagogastric junction, clinical stage T2-4N0-3M0, ECOG performance status 0-1, and adequate major organ function. All patients received 3 cycles of neoadjuvant therapy consisting of: tislelizumab (200 mg, D1, Q3W), oxaliplatin (130 mg/m², D1, Q3W), and S-1 (40-60mg based on BSA, po, bid, D1-14, Q3W). Following efficacy evaluation, patients underwent resection of the esophagogastric junction adenocarcinoma 4-8 weeks after completion of neoadjuvant therapy. The primary endpoint is pathologic complete response (pCR). Secondary endpoints include major pathologic response (MPR), objective response rate, R0 resection rate, overall survival (OS), disease-free survival (DFS), and safety. Results: As of June 2025, a total of 40 patients were enrolled in this study. The median age was 66 years (range, 37-76), 87.5% were male, and 92.5% had an ECOG performance status of 0. Among them, 87.5% (n = 35) of the patients completed 3 cycles of neoadjuvant therapy. The remaining 5 cases completed 1 (n = 1, due to grade≥3 TRAEs), 2 (n = 2, due to grade≥3 TRAEs and patient decision, respectively), and 4 (n = 2, patient decision) cycles of treatment. All patients underwent resection of the esophagogastric junction adenocarcinoma. The R0 resection rate was 97.5% (39/40), with no patients requiring re-operation or experiencing perioperative mortality. The pathologic complete response (pCR) rate was 25% (10/40). The primary tumor pCR rate reached 30% (12/40), and the major pathologic response (MPR) rate was 37.5% (15/40). Treatment-related adverse events (TRAEs) of any grade occurred in 95% (38/40) of patients, with grade ≥3 TRAEs observed in 15% (6/40). Conclusions: Neoadjuvant therapy with Tislelizumab in combination with oxaliplatin and S-1for locally advanced Siewert type Ⅱ esophagogastric junction adenocarcinoma yields a favorable pathological complete response (pCR) rate and shows a good safety profile. Clinical trial information: ChiCTR2300075638.

OBJECTIVE:To investigate the distribution patterns and dissection efficacy of lymph node metastasis in thoracic esophageal cancer, providing a theoretical basis for standardized lymphadenectomy during esophageal cancer surgery. METHODS:A total of 703 patients who underwent radical resection for thoracic esophageal cancer via the right thoracic approach at the Fourth Hospital of Hebei Medical University between January 2014 and March 2023 were analyzed. According to tumor location, patients were classified into upper, middle, and lower thoracic groups. Lymph nodes were categorized anatomically into three regions: upper mediastinum, lower mediastinum, and upper abdomen. Stratified analyses were performed according to tumor invasion depth (T stage) and histological differentiation grade. Metastasis rates and efficacy index (EI) values were calculated for each lymph node station to clarify correlations between tumor characteristics and nodal involvement and to assess the impact of metastatic stations on patient survival. RESULTS:Overall metastasis rates to the upper mediastinal, lower mediastinal, and upper abdominal lymph nodes were 37.55%, 18.07%, and 23.33%, respectively. Among all stations, the right recurrent laryngeal nerve lymph nodes (Station 106recR) exhibited the highest metastasis rate (22.62%) and EI (11.22). Metastasis to lymph nodes along the hepatic artery (Station 8a), celiac axis (Station 9), and proximal splenic artery (Station 11p) was extremely low (≤0.85%). Stratified analysis showed that in upper and middle thoracic cancers, metastasis was most frequent at Station 106recR, with both the metastasis rates and EI increasing with greater tumor invasion invasion (T3-T4 vs. T1-T2) and poorer differentiation. For example, in upper thoracic cancer with T3-T4 poorly differentiated tumors, Station 106recR had a metastasis rate of 44.44% and an EI of 22.22. In lower thoracic cancers, perigastric lymph nodes (Stations 1-4) had the highest metastasis rate (24.71%) and EI (10.08). Among T1-T2 tumors, moderately-to-well differentiated cases metastasized predominantly to Station 106recR (7.69%, EI 5.13), whereas poorly differentiated tumors primarily involved the left gastric artery nodes (Station 7; 33.33%, EI 12.50). In T3-T4 poorly differentiated lower thoracic tumors, perigastric nodes showed the highest metastasis (59.46%, EI 22.31). CONCLUSION:Lymph node metastasis in thoracic esophageal cancer exhibits distinct, site-specific patterns. Upper and middle thoracic tumors predominantly metastasize upward to recurrent laryngeal nerve nodes, whereas lower thoracic tumors primarily involve the perigastric region. The risk and extent of lymph node metastasis-including the number of involved nodes, nodal stations, and EI values-increase with deeper invasion and poorer differentiation. Although distant lymph node metastasis occurs frequently in advanced disease, an EI of zero indicates no survival benefit from extended lymphadenectomy. Surgical lymphadenectomy should therefore be individualized based on tumor location, invasion depth, differentiation, and nodal metastatic patterns.

BackgroundThis large retrospective study aimed to compare the long-term survival outcomes of esophageal squamous cell carcinoma (ESCC) patients with stage T4N0-3M0 treated with surgery followed by adjuvant chemoradiotherapy (S+CRT) versus definitive chemoradiotherapy (dCRT).MethodsPatients with T4N0-3M0 ESCC who received S+CRT or dCRT at our institution between January 2011 and December 2018 were included in the study.ResultsA total of 490 patients with stage T4N0-3M0 ESCC met the enrollment criteria, with 108 in the S+CRT group and 382 in the dCRT group. Overall survival (OS) and progression-free survival (PFS) were significantly better in S+CRT group compared to the dCRT group (P = 0.000, 0.003). After propensity score matching (PSM) analysis, 138 patients in the dCRT group and 81 patients in the S+CRT group were successfully matched. OS and PFS were again significantly better in the S+CRT group compared to the dCRT group (P = 0.002, 0.019).ConclusionsS+CRT is more likely to improve the overall prognosis of patients with T4N0-3M0 ESCC compared to dCRT. Treatment plan should be made based on a thorough consideration of both the patient’s condition and tumor characteristics, leading to individualized decisions.

Background:Esophageal squamous cell carcinoma (ESCC) lacks reliable prognostic biomarkers. Homologous recombination deficiency (HRD) has been implicated in genomic instability across multiple cancers, but its prognostic significance in ESCC remains unexplored. This study aimed to evaluate HRD score as a prognostic biomarker and develop a machine learning-based predictive model for ESCC. Methods:Transcriptomic and clinical data from 78 ESCC patients were obtained from The Cancer Genome Atlas (TCGA) and randomly split into training (70%) and test (30%) cohorts. Prognostic models were constructed using 112 machine learning algorithm combinations based on DNA damage response (DDR)-related genes. Gene set enrichment analysis (GSEA), somatic mutation profiling, and immune cell infiltration estimation via CIBERSORT were performed to characterize HRD-associated molecular features. Results:High HRD scores were significantly associated with poorer overall survival (P<0.05). Among 112 algorithm combinations, the survival support vector machine (Survival-SVM) model demonstrated optimal performance [training concordance index (C-index): 0.741; test C-index: 0.708], identifying six hub genes: PARP1, MBD4, TELO2, NSMCE3, SMUG1, and BABAM1. A nomogram incorporating risk score (RS) and clinical variables achieved strong predictive accuracy for 1- to 3-year survival [area under the curve (AUC) >0.7]. High-HRD tumors exhibited distinct mutational patterns (TP53 and TTN) and enriched glutathione metabolism and cytochrome P450 pathways. Immune infiltration analysis revealed significant differences in plasma cell and neutrophil infiltration between risk groups (P<0.05), suggesting HRD-associated immune microenvironment remodeling. Conclusions:We developed a novel HRD-based prognostic model incorporating six DDR-related genes that demonstrates robust predictive performance in ESCC. HRD score is identified as an independent prognostic factor associated with genomic instability, immune microenvironment alterations, and clinical outcomes. These findings provide a theoretical basis for personalized treatment strategies, including potential applications of PARP inhibitors and immunotherapy in ESCC.

BackgroundT4 esophageal squamous cell carcinoma (ESCC) is associated with dismal prognosis, and the optimal treatment remains uncertain. This study aimed to identify the clinical and pathological characteristics of T4 ESCC patients in China and compare the efficacy, adverse events, and treatment failure patterns of two treatment strategies: neoadjuvant chemotherapy followed by surgery and adjuvant chemoradiotherapy (nCT+S) or neoadjuvant chemotherapy followed by definitive chemoradiotherapy (nCT+dCRT).MethodsWe retrospectively analyzed the clinical records of 1242 cT4N0-3M0 ESCC patients from January 2015 to December 2020. After performing propensity score matching (PSM), a total of 195 patients were included in the analysis, comprising 73 patients in the nCT+S group and 122 in the nCT+dCRT group. To address potential selection bias related to resectability, we further performed a subgroup analysis limited to MDT-confirmed resectable T4 ESCC patients after nCT.Endpoints included overall survival (OS), progression-free survival (PFS), and related clinical outcomes.ResultsThe median follow-up time was 77.0 months (95% CI: 68.1-85.9). For the entire post-propensity score matching (PSM) cohort, the 1-, 3-, and 5-year overall survival (OS) rates were 65.6%, 27.6%, and 17.4%, respectively, with a median OS of 18.0 months (95% CI:14.9-21.1); the corresponding 1-, 3-, and 5-year progression-free survival (PFS) rates were 49.7%, 22.6%, and 14.5%, with a median PFS of 12.0 months (95% CI:8.8-15.2).Multivariate Cox regression analysis confirmed that treatment modality (nCT+S vs nCT+dCRT) and N stage were independent prognostic factors for both OS (HR = 1.867, 95% CI:1.341-2.598;HR=1.595, 95% CI:1.286-1.977, both P<0.001) and PFS (HR = 1.576, 95%CI:1.146-2.167; HR = 1.741, 95%CI:1.286-1.977, both P<0.01).After Bonferroni correction for multiple testing (corrected α=0.0025), subgroup analysis demonstrated that patients with ECOG performance status 0-1, cT4a stage, cN0 stage, and mid-esophageal tumors derived significant OS benefits from nCT+S (all P<0.0025);for PFS, male patients, those aged >64 years, with tumor length >5.0 cm, cT4a stage, cN0 stage, and mid-esophageal tumors obtained significant benefits from nCT+S (all P<0.0025).In the subgroup restricted to MDT-assessed resectable T4 lesions after nCT, nCT+S still provided significantly superior OS and PFS versus nCT+dCRT (both P<0.0025 after Bonferroni correction).Notably, the incidence of severe treatment-related complications was significantly lower in the nCT+S group (4.1%, 3/73) than in the nCT+dCRT group (18.9%, 23/122; χ²=8.591, P = 0.003).Additionally, the rate of isolated local or regional lymph node recurrence was significantly higher in the nCT+dCRT group (χ²=7.348, P = 0.007), though the overall treatment failure rate showed no statistical difference between the two groups.ConclusionIn nCT-responsive, MDT-evaluated resectable or downstaged resectable cT4N0-3M0 ESCC, nCT+S achieves longer OS and PFS than nCT+dCRT, with more survival benefits in ECOG 0-1, cT4a, cN0 or mid-esophageal tumor subgroups; it also lowers severe complications and isolated local/regional recurrence risk.These results were validated in a resectable-only subgroup, minimizing selection bias related to tumor resectability.Large multicenter randomized trials are required to validate these findings and define optimal therapy for T4 ESCC due to single-center retrospective limitations.

Background:Esophageal cancer (EC) is the eighth most prevalent malignancy worldwide and exhibits the sixth poorest prognosis. Esophageal squamous cell carcinoma (ESCC) is the predominant pathological subtype. Ferroptosis, an iron-dependent form of cell death, plays a critical role in cancer progression. Long non-coding RNAs (lncRNAs) have emerged as key regulators in the initiation and progression of EC. However, the role of lncRNAs in modulating ferroptosis within EC remains poorly understood. Therefore, this study aimed to identify key ferroptosis-related lncRNAs in ESCC and to investigate the role and mechanism of a specific lncRNA, long intergenic non-protein-coding RNA 92 (LINC00092). Methods:Bioinformatics analysis was conducted to identify ferroptosis-related lncRNAs, transcription factors (TFs), and genes associated with ESCC. The expression, function, tumor microenvironment, immunotherapy, and downstream molecular pathways were also determined. The expression levels of LINC00092, MYC-associated zinc finger protein (MAZ), and NFE2 like bZIP transcription factor 2 (NFE2L2) were detected using quantitative real-time polymerase chain reaction (qRT-PCR), immunohistochemical analysis, and western blotting. Fluorescence in situ hybridization (FISH) was performed to determine the subcellular localization of LINC00092. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), colony formation, wound healing, Transwell, and flow cytometry apoptosis assays were performed to determine the phenotypes and functions of loss- and gain-of LINC00092. RNA immunoprecipitation (RIP) and luciferase reporter assays were used to evaluate interactions involving LINC00092. The expression of ferroptosis-related proteins was verified by western blotting. Results:LINC00092 was found to be downregulated in ESCC datasets, cell lines, and tissue samples. Bioinformatics analysis revealed that LINC00092 was associated with ferroptosis and negatively correlated with NFE2L2 expression. Further investigations demonstrated that LINC00092 acted as a binder to the TF MAZ, modulating the expression of the ferroptosis-related gene NFE2L2. Overexpression of LINC00092 inhibited ESCC cell progression, whereas its downregulation promoted tumor progression. RIP and luciferase reporter assays confirmed that MAZ was a target of LINC00092, and NFE2L2 was a downstream target of MAZ. Western blot analysis showed that LINC00092 enhanced ferroptosis in ESCC cells. The LINC00092/MAZ/NFE2L2 axis appeared to inhibit cancer progression by promoting ferroptosis through the regulation of NFE2L2 and sequestration of the TF MAZ. Conclusions:LINC00092 exerts tumor-suppressive effects in ESCC cells by inhibiting cancer progression through the LINC00092/MAZ/NFE2L2 axis and promoting ferroptosis. Therefore, LINC00092 may serve as a potential therapeutic target for ESCC.

Developing personalized treatment plans in cancer care is a complex and time-intensive process. The multidisciplinary Molecular Tumor Board (MTB) approach offers a promising solution for tailoring precision treatments but is often limited by the manual analysis of vast molecular data, which is laborious and error-prone. To address these challenges, we developed SmartMTB, an artificial intelligence (AI)-based assistant, designed to support clinicians in formulating cost-effective and efficient personalized treatment plans. SmartMTB leverages a medical-field-customized large-language model and a database tailored to the Chinese population. It integrates patient-specific tumor types and gene variation data to suggest personalized treatment strategies. In a real-world, multi-center retrospective study on the precision medicine platform, we included clinical data of 1032 Chinese cancer patients and asked SmartMTB for treatment plan suggestions. The study cohort included 1,032 patients spanning 13 major tumor types, with a median age of 58 years (range: 7-87 years). Clinical stages ranged from I to IV (stage I: 11.4%, stage II: 10.3%, stage III: 21.9%, stage IV: 51.6%, unknown: 4.8%). Among them, 92% of the patients got treatment plan suggestions from SmartMTB. Eventually, 39.4% of the patients received SmartMTB-recommended treatment plans, while 52.5% did not. Patients who received SmartMTB-recommended treatment plans exhibited higher partial response rate (PR, 31.4% vs. 11.3%), objective response rate (ORR, 34.1% vs. 12.3%) and longer median progression-free survival (mPFS, 163 vs. 92 days, P < 0.0001) than those who did not. Similar benefits were observed across cancer types, including lung cancer (PR: 31.9% vs. 10.2%; ORR: 35.2% vs. 11.9%; mPFS: 185 vs. 92 days, P < 0.0001) and hepatobiliary tumors (PR: 28.6% vs. 13.3%; ORR: 31.4% vs. 15%; mPFS: 121 vs. 87 days, P = 0.024). Excluding lung cancer patients treated with EGFR-TKI, SmartMTB's recommendations maintained efficacy for the remaining lung cancer patients (PR: 31.7% vs. 8.9%; ORR: 35% vs. 10.7%; mPFS: 153 vs. 90 days, P < 0.0001). Furthermore, SmartMTB took about 2.5 h to analyze data from 1032 patients and provide treatment suggestions, which was much more efficient than the traditional manual MTB. In this study, patients using treatment strategy SmartMTB recommended had much better clinical treatment results than those who didn't. This study highlights the clinical utility of SmartMTB in enhancing treatment outcomes for cancer patients. By providing timely, accurate, and personalized treatment recommendations, SmartMTB addresses critical gaps in traditional approaches, reducing time and cost burdens. Its potential for widespread clinical adoption could transform precision oncology practices and improve patient care globally. Minghui Wang, Yanhong Shang, Zhengang Yuan, Xin Huang, Qing Hao, Shaohua Yuan, Guobang Shi, Hui Chen, Wenjin Liu, Lili Wang, Shiwang Wen, Huilai Lv, Zhizheng Wang, Dong You, Yang Liu, Fei Pang, Wei Rao, Haitao Wang, Leilei Lu, Kai Wang. AI-based MTB assistant in cancer personalized treatment: Analysis from a real-world, multi-center retrospective study. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 3650.

To evaluate the clinical efficacy of Grunenwald incision in cervicothoracic junction surgery. Methods: A retrospective analysis was performed on 29 patients treated at the Fourth Hospital of Hebei Medical University, including 28 patients with cervicothoracic junction tumors (11cases of upper mediastinal tumors, 7 cases of superior sulcus tumors, 4 cases of thyroid tumors with upper mediastinal invasion, 4 cases of chest wall tumors, 2 cases of esophageal cancers with supraclavicular lymph node metastasis) and 1 patient with cervicothoracic junction penetrating trauma. Grunenwald incision or additional posterolateral thoracic incision, median sternal incision or neck collar incision were used in all patients. There was no perioperative death in the whole group. Complete tumor resection was achieved in 25 cases; palliative resection was performed in three cases, and one case underwent complete foreign body removal. The operation time ranged from 120 to 430 minutes, with an average of (231.90 ± 85.30) minutes. The intraoperative blood loss was between 100 and 1000 milliliters, with an average of (286.56 ± 192.90) milliliters. The postoperative hospital stay lasted 6 to 28 days, with an average of (13.14 ± 5.12) days. Follow-up periods spanned 6 to 142 months, with an average of (66.66 ± 46.96) months. During the follow-up period, six patients died. Grunenwald incision can provide good exposure of the structures near the cervicothoracic junction, preserve the integrity of the sternoclavicular joint, reduce shoulder deformity, and has advantages for patients with cervicothoracic junction tumor, high rib resection, and cervicothoracic junction trauma.

Objective:To investigate the influence of the depth of invasion on the prognosis of pT1 stage mid-thoracic esophageal cancer patients undergoing left thoracotomy.Methods:Retrospectively analyze the clinicopathological data of 139 patients with pT1N0M0 stage of mid-thoracic esophageal cancer who meet the enrollment criteria. Firstly, the prognosis and influencing factors of the whole group were analyzed. The differences in prognosis, local recurrence and distant metastasis between PT1A and PT1B patients were compared, and the influence of different infiltration depth on prognosis and treatment failure of patients was analyzed. SPSS 19.0 statistical software was used for statistical analysis.Results:The 1-year, 3-year and 5-year overall survival(OS) and disease-free survival(DFS) were 95.0%, 87.8%, 82.0% and 91.4%, 84.2%, 77.0%, respectively. There were significant differences in OS( χ2=7.500, P=0.006) and DFS( χ2=7.354, P=0.007) at 1, 3 and 5 years between pT1a and pT1b patients. Cox multivariate analysis showed that pT stage and pathological type were independent prognostic factors for OS and DFS( P<0.05). There were no significant differences in OS( χ2=0.734, P=0.693) and DFS( χ2=0.7690, P=0.681) of pT1a tumors with different invasion depths. There were significant differences in OS( χ2=15.368, P<0.001) and DFS( χ2=27.470, P<0.001) at 1, 3 and 5 years of pT1b tumors with different invasion depths. The recurrence rate of pT1b(23.8%) was significantly higher than that of pT1a(5.3%)( χ2=5.274, P=0.022). The distant metastasis rate of the former(10.9%) was also significantly higher than that of the latter(0)( χ2=4.494, P=0.034). There were significant differences in local recurrence rate( χ2=17.051, P<0.001) and distant metastasis rate( χ2=15.460, P<0.001) among pT1b patients with different infiltration depths. Logistic multivariate analysis showed that the depth of infiltration was an independent factor affecting the occurrence of local recurrence in stage pT1b patients after treatment( P<0.001). Pathological type( P=0.003) and infiltration depth( P=0.027) were independent factors affecting the occurrence of distant metastasis. Conclusion:pT1a period and pT1b period after the prognosis and treatment of patients with different failure modes, and pT1b period in patients with different infiltration depth and the prognosis of patients and its failure mode after treatment significantly related, infiltration depth of pT1b period after treatment in patients with the independence of the influencing factors of failure, suggest that clinical doctors should pay attention to pT1b period in patients with postoperative adjuvant therapy. This conclusion needs to be confirmed by large prospective studies of cases.

Objective:To exploring risk factors for perioperative respiratory complications in minimally invasive esophagectomy esophagectomy for esophageal cancer.Methods:A total of 100 patients with squamous esophageal cancer who were underwent total laparoscopic radical esophageal cancer surgery in the Fourth Hospital of Hebei Medical University from January 2021 to October 2022 were retrospectively included as study subjects, and all patients were divided into no-complication group(n=73)and complication group(n=27)according to whether or not they developed respiratory complications during the perioperative period.The baseline and surgery-related data of the patients were pooled and analyzed, and unifactorial and multifactorial logistic regression were applied to analyze the independent risk factors for the occurrence of respiratory complications during the perioperative period of total laparoscopic radical esophageal cancer surgery.Results:Among the 100 patients with squamous esophageal cancer who were underwent total laparoscopic radical esophageal cancer surgery, 27 patients developed respiratory complications during the perioperative period, including 1 patient with tracheal and bronchial injury, 9 patients with hoarseness accompanied by lung infections, 17 patients with pneumonia.There were no statistically significant differences in gender, body mass index, disease duration, history of alcohol consumption, history of hypertension, tumor location, pathological stage, intraoperative bleeding volume, intraoperative intercostal nerve block, and number of lymph node dissection between the complication group and the non-complication group(P>0.05). There were statistically significant differences in age, smoking history, preoperative diabetes mellitus, preoperative chronic obstructive pulmonary disease(COPD), intraoperative fluid infusion volume, operation time, intraoperative thoracic adhesion, and intraoperative recurrent laryngeal nerve injury between the complication group and the non-complication group(P<0.05). The results of multifactorial logistic regression analysis showed that age≥65 years, history of smoking, preoperative diabetes mellitus, preoperative COPD, intraoperative thoracic adhesions, and intraoperative recurrent laryngeal nerve injury were the independent risk factors for the occurrence of perioperative respiratory complications in total laparoscopic radical surgery for esophageal cancer.Conclusion:Perioperative respiratory complications during total laparoscopic radical surgery for esophageal cancer are closely related to age≥65 years, smoking history, preoperative diabetes mellitus, preoperative COPD, intraoperative thoracic adhesion, intraoperative recurrent laryngeal nerve injury.We can better prevent the above risk factors, reduce the occurrence of perioperative respiratory complications, and improve the prognosis of patients by performing nebulization, control of blood glucose levels, and neuroprotection during operation.

Background:The study aimed to clarify the characteristics of lymph node metastasis (LNM) and to compare the oncologic outcomes of minimally invasive esophagectomy (MIE) with open esophagectomy (OE) in terms of lymph node dissection (LND) in thoracic esophageal cancer patients.Methods:The data from esophageal cancer patients who underwent MIE or OE from January 2016 to January 2019 were retrospectively reviewed. The characteristics of LNM in thoracic esophageal cancer were discussed, and the differences in numbers of LND, LND rate, and LNM rate/degree of upper mediastinum between MIE and OE were compared.Results:For overall characteristics of LNM in 249 included patients, the highest rate of LNM was found in upper mediastinum, while LNM rate in middle and lower mediastinum, and abdomen increased with the tumor site moving down. The patients were divided into MIE (n = 204) and OE groups (n = 45). In terms of number of LND, there were significant differences in upper mediastinum between MIE and OE groups (8 [5, 11] vs. 5 [3, 8], P < 0.001). The comparative analysis of regional lymph node showed there was no significant difference except the subgroup of upper mediastinal 2L and 4L group (3 [1, 5] vs. 0 [0, 2], P < 0.001 and 0 [0, 2] vs. 0, P = 0.012, respectively). Meanwhile, there was no significant difference in terms of LND rate except 2L (89.7% [183/204] vs. 71.1% [32/45], P = 0.001) and 4L (41.2% [84/204] vs. 22.2% [10/45], P = 0.018) groups. For LNM rate of T3 stage, there was no significant difference between MIE and OE groups, and the comparative analysis of regional lymph node showed that there was no significant difference except 2L group (11.1% [5/45] vs. 38.1% [8/21], P = 0.025). The LNM degree of OE group was significantly higher than that of MIE group (27.2% [47/173] vs. 7.6% [32/419], P < 0.001), and the comparative analysis of regional LNM degree showed that there was no significant difference except 2L (34.7% [17/49] vs. 7.7% [13/169], P < 0.001) and 4L (23.8% [5/21] vs. 3.9% [2/51], P = 0.031) subgroups.Conclusion:MIE may have an advantage in LND of upper mediastinum 2L and 4L groups, while it was similar to OE in other stations of LND.

BACKGROUND:Video assisted thoracic surgery (VATS) is the main surgical method for lung cancer. The aim of this study was to analyze the reasons for conversion to thoracotomy in 83 cases among 1,350 consecutive cases who underwent video-assisted thoracic surgery (VATS) lobectomy by a single surgical team, in order to achieve a deeper understanding of the rules and the opportunity for conversion to thoracotomy in VATS lobectomy under normal conditions.METHODS:The clinical data of 1,350 patients who underwent VATS lobectomy between September 21, 2009 and June 1, 2020, by a single surgical team in the Fifth Department of Thoracic Surgery of the Fourth Hospital of Hebei Medical University were retrospectively analyzed. There were 773 males and 577 females, aged 8-87 years, with a median age of 61.3 years, including 83 cases of benign diseases, 38 cases of lung metastases, and 1,229 cases of primary lung cancer. The cases with stage I, II and IIIa were 676, 323 and 230, respectively. The cases of left upper, left lower, right upper, right middle, right lower, right middle and upper and right middle and lower lobectomy were 301 (22.30%), 231 (17.11%), 378 (28.00%), 119 (8.81%), 262 (19.41%), 16 (1.19%) and 43 (3.19%), respectively.RESULTS:In the cohort of 1,350 consecutive patients with VATS lobectomy, 83 patients (6.15%) were converted to thoracotomy for different reasons. The conversion rate of benign lesions was significantly higher than that of malignant tumors (P<0.05). The conversion rate in stage IIIa was significantly higher than that in stage I and II (P<0.05). The conversion rate of combined lobectomy was significantly higher than that of single lobectomy (P=0.001). The conversion rate of left upper lobectomy was significantly higher than that of other single lobectomy (P<0.001). The conversion rate of right middle lobectomy was significantly lower than that of other single lobectomy (P=0.049). The main reasons for conversion were vascular injury (38.55%), lymph node interference (26.51%) and dense adhesion in thoracic cavity (16.87%). In the conversion group, the total operation time was (236.99±66.50) min and the total blood loss was (395.85±306.38) mL. The operation time in patients converted to thoracotomy due to lymph node interference was (322.50±22.68) min, which was significantly longer than that in the other groups (P<0.05). The intraoperative blood loss in patients converted to thoracotomy due to vascular injury was (560.94±361.84) mL, which was significantly higher than that in the other groups (P<0.05). With the increase in surgical experience, the number of vascular injuries gradually decreased at the early stage, mid-stage and late stage (P=0.045).CONCLUSIONS:In VATS lobectomy, benign lung lesions and more advanced malignant tumors led to more surgical difficulties and higher conversion rate. The conversion rate was different in different lobectomy sites, with the highest in left upper lobectomy, and the lowest in right middle lobectomy. Vascular injury, lymph node interference and dense adhesion were the main reasons for conversion to thoracotomy, which led to prolonged operation time and increased blood loss. With the increasing number of surgical cases, the rate of conversion to thoracotomy in VATS lobectomy continues to decline, which may be mainly due to the more advanced treatment of pulmonary vessels.

This study investigates whether minimally invasive esophagectomy (MIE) is a safe and effective way for patients with resectable esophageal cancer by comparing the short-term quality of life (QOL) after minimally invasive esophagectomy and open esophagectomy (OE). A total number of 104 patients who underwent esophagectomy from January 2013 to March 2014 were enrolled in this study. These patients were divided into two groups (MIE and OE group). Three scoring scales of quality of life were used to evaluate QOL before the operation and at the first, third, sixth and twelfth months after MIE or OE, which consist of Karnofshy performance scale (KPS), the European Organization for Research and Treatment questionnaire QLQC-30 (EORTC QLQC-30) and esophageal cancer supplement scale (OES-18). The MIE group was higher than the OE group in one-year survival rate (92.54% vs. 72.00%). Significant differences between the two groups were observed in intraoperative bleeding volume (158.53 ± 91.07 mL vs. 228.97 ± 109.33 mL, p = 0.001), and the incidence of postoperative pneumonia (33.33% vs. 58.62%, p = 0.018). The KPS of MIE group was significantly higher than the OE group at the first (80 vs. 70, p = 0.004 < 0.05), third (90 vs. 80, p = 0.006 < 0.05), sixth (90 vs. 80, p = 0.007 < 0.05) and twelfth months (90 vs. 80, p = 0.004 < 0.05) after surgery. The QLQC-30 score of MIE group was better than OE group at first and twelfth months after the operation. The OES-18 score of MIE group was significantly better than OE group at first, sixth and twelfth months after surgery. The short-term quality of life in MIE group was better than OE group.

目的:探讨miR-627-3p在食管鳞状细胞癌(esophageal squamous cell carcinoma,ESCC)组织中的表达及其对ESCC细胞生物学行为的影响.方法:收集2015年1月至2015年10月河北医科大学第四医院胸外科手术切除的ESCC组织86例及对应的癌旁组织标本20例.通过qPCR法检测miR-627-3p在86例ESCC组织及癌旁组织中的表达,分析其表达与ESCC患者临床病理学指标及预后的关系;利用Kaplan-Meier Plotter在线数据库进一步分析数据库中hsa-miR-627的表达与ESCC患者预后的关系;通过qPCR法检测miR-627-3p在4株ESCC细胞系中的表达,选取表达水平最低的食管癌细胞转染miR-627-3p mimic,选取表达水平最高的ESCC细胞转染miR-627-3p inhibitor,采用CCK-8法检测细胞的增殖,采用Transwell实验检测细胞迁移和侵袭;采用KEGG分析探讨miR-627-3p可能介导的信号转导通路,并采用qPCR法验证miR-627-3p对信号通路中关键基因表达的影响.结果:miR-627-3p在ESCC组织中的表达明显低于在癌旁组织中的表达,miR-627-3p的表达与ESCC患者淋巴结转移和临床分期相关(均P＜0.05);miR-627-3p高表达的ESCC患者的5年生存率明显高于miR-627-3p低表达的食管癌患者(P＜0.05).ESCC细胞系KYSE170中miR-627-3p表达最低,KYSE30中miR-627-3p表达最高;在KYSE170细胞中转染miR-627-3p mimic后,细胞的增殖能力无明显变化(P＞0.05),但细胞的迁移(P＜0.05)和侵袭能力(P＜0.05)显著降低;在KYSE30细胞中转染miR-627-3p inhibitor后,细胞的增殖能力无明显变化(P＞0.05),但细胞的迁移(P＜0.05)和侵袭能力(P＜0.05)显著增高.KEGG分析结果显示,miR-627-3p介导了多条与肿瘤相关的信号转导通路.结论:miR-627-3p在ESCC组织中的表达明显低于在癌旁组织中的表达,其低表达与ESCC患者的不良预后相关,miR-627-3p抑制ESCC细胞的迁移和侵袭,可能是通过干扰多条与肿瘤相关的信号通路发挥生物学功能.

Abstract Background: Immune checkpoint inhibitors (ICIs) have provided remarkable antitumor effects in non-small cell lung cancer (NSCLC), and 5 PD-1 inhibitors have been approved in China. Several studies showed that NSCLC patients with oncogenic driver mutations may have poor responses to ICIs. However, the role of immunotherapy in oncogene-addicted NSCLC remains unclear and the relationship between PD-L1 expression, TMB, and driver gene mutations is not fully understood. Methods: Formalin-fixed, paraffin-embedded (FFPE) tumor tissue and matched blood samples of 1111 NSCLC patients from OrigiMed were collected for targeted NGS panel sequencing from December 2017 to January 2019. Genomic alterations (GAs) including single nucleotide variations, short and long insertions/deletions, copy number variations, and gene rearrangements were assessed. Tumor mutational burden high (TMB-H) was defined as ≥10 muts/Mb. PD-L1 expression positivity was defined as ≥1% of tumor cells with membranous staining (22C3, DAKO). Results: We found EGFR GAs in 59.4% of patients (660/1111) in the OrigiMed database, including 249 ex19del, 291 L858R, 31 ex20ins, 33 G719X, 30 T790M, 11 L861Q, and 15 other uncommon mutations. The frequency of EGFR mutations was significantly higher in female patients (p<0.001) and non-smoker patients (p<0.001). EGFR mutations were associated with a significantly lower TMB compared with wild-type (3.7 vs. 6.9 muts/Mb, respectively, p<0.001). However, EGFR G719X was correlated with a significantly higher TMB and TMB-H/PD-L1-positive proportion than EGFR ex19del (p<0.001) and L858R (p<0.001). In addition, the frequency of concurrent TERT GAs with EGFR ex19del and L858R was higher than that with EGFR G719X (p=0.017), while the frequency of concurrent LRP1B and MED12 GAs with EGFR G719X was higher than that with EGFR ex19del and L858R (p=0.009 and p=0.008, respectively). Furthermore, the frequency of concurrent gene copy number amplification with EGFR ex19del and L858R was higher than that with EGFR G719X (p=0.086 and p=0.037, respectively). Conclusion: This study's findings reveal that different EGFR mutation subtypes display heterogeneous immunotherapeutic features, and EGFR G719X was associated with an increased TMB, a higher proportion of TMB-H/PD-L1 positive patients, and fewer concurrent copy number amplification GAs. This suggests that GAs of G719X may have implications as a biomarker for guiding ICI treatment in EGFR-mutated NSCLC. Citation Format: Yanhong Shang, Ziqiang Tian, Shiwang Wen, Jie Yang, Jian Guo, Mingjiang Li, Dan Liu, Shiyue Zhang, Kai Wang. Different subtypes of EGFR mutations exhibit distinct patterns of TMB and PD-L1 in patients with non-small cell lung cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5886.

e16678 Background: Biliary tract cancers (BTCs) are a group of relatively rare invasive carcinomas including gallbladder carcinoma (GBC), intrahepatic (ICC), hilar (HCCA), and extrahepatic (ECC) cholangiocarcinoma. In the ROAR basket trial, dabrafenib, a BRAF inhibitor, combined with trametinib, a MEK inhibitor, demonstrated promising efficacy in patients with BTCs with an overall response rate (ORR) of 41% and a favorable safety profile. The frequency of BRAF mutations reported in BTC varies widely, and BRAF V600E mutations have been reported in 0% to 20% of BTCs. However, the frequencies of BRAF mutations in Chinese BTCs are not clear. Methods: A total of 926 BTC patients (203 ECC, 195 GBC, 59 HCCA, and 469 ICC) were included in this study. Formalin-fixed, paraffin-embedded (FFPE) tumor tissues and matching blood samples from these patients were collected and sequenced using next-generation sequencing (NGS) targeting 450 cancer genes. Genomic alterations including single nucleotide variants, insertions and deletions, copy number variations, and fusions were assessed. The testing was carried out by a College of American Pathologists (CAP) accredited and Clinical Laboratory Improvement Amendments (CLIA) certified laboratory. Results: BRAF activating mutations were detected in 5.5% of Chinese BTC patients. There were 5.1% in ICC cases, 8.9% in ECC cases, 5.1% in HCCA cases, and 3.1% in GBC cases. BRAF V600E, the most common hotspot mutation, was detected in ICC and GBC with frequencies of 1.5% and 0.5%, respectively. No BRAF V600E was detected in ECC or HCCA. The top-ranked co-mutation genes with BRAF were TP53 (54%), ARID1A (40%), and SMAD4 (32%). Compared with BRAF wild-type cohort, the frequencies of ARID1A and SMAD4 mutations were significantly higher in patients with BRAF mutations cohort (40% vs 17%, P< 0.001; 32% vs 14%, P< 0.001), while KRAS mutations were mutually exclusive with BRAF mutations. Conclusions: To our knowledge, this is the largest BTCs cohort used to study the characterization of BRAF mutations in the Chinese patients. BRAF mutations occurred in 5.5% of patients, and BRAF V600E in 0.9%. These patients could benefit from treatment with a BRAF inhibitor combined with a MEK inhibitor. Analysis of BRAF V600E should be considered in patients with BTCs, especially in ICC and GBC. Clinical trial information: NCT03892577 .

Objective:To detect the serum microRNA (miRNA, miR)-28 levels in patients with esophageal cancer, and to investigate its clinical usefulness.Methods:Three groups of subjects were selected: 90 cases of esophageal cancer patients with an initial diagnosis who have accepted radical operation as the initial diagnosis group, 30 cases of patients with esophageal cancer recurred after the surgery as the recurrence group, and 60 cases of healthy volunteers receiving the health examination as the control group. Levels of serum miR-28, sterol regulatory element binding factor 2 (SREBF2), and homeobox B3 (HOXB3) mRNA were tested by real-time quantitative polymerase chain reaction (Real-time PCR). The receiver operating characteristic (ROC) curve of serum miR-28 in the initial diagnosis group and the recurrence groups was drawn. t-test, ANOVA, χ2 test, and receiver operating characteristic curve (ROC) were used to analyze data of results via SPSS 26.0 statistical software. Results:The serum miR-28 levels in the recurrence group, the initial diagnosis group and the control group were (0.275±0.084), (0.337±0.186) and (0.878±0.174) respectively. There were significant differences in MiR-28 levels among three groups ( P<0.01). Levels of serum SREBF2 and HOXB3 mRNA in the recurrence group (1.005±0.199, 0.814±0.113) and initial diagnosis group (0.950±0.175, 0.755±0.104) were significantly higher than in the control group (0.264±0.074, 0.332±0.092, F=76.589, 54.821, P<0.01). The miR-28 levels in the initial diagnosis group increased significantly (0.853±0.186) after surgery ( t=4.014, P<0.01), and those of SREBF2 and HOXB3 mRNA were reduced significantly (0.297±0.085, 0.334±0.090, t=-11.337, -9.064, P<0.01). Spearman’ s correlation showed that there was negatively correlation between miR-28 and SREBF2 mRNA, or between miR-28 and HOXB3 mRNA in the initial diagnosis group before surgery ( r=-0.669, -0.268, P<0.05), but there was no obvious correlation between the serum miR-28 and SREBF2 mRNA, or between miR-28 and HOXB3 mRNA in the recurrence group ( r=0.010, -0.225, P>0.05). The area under the ROC curve (AUC) in the initial diagnosis group and the recurrence group was 0.691 and 0.935 respectively. Conclusion:The serum miR-28 level in esophageal cancer patients was significantly lower than in healthy people. The determination of serum miR-28 levels could be useful to diagnose esophageal cancer and predict the recurrence. The miR-28 could participate in the development and recurrence of esophageal cancer through inhibiting SREBF2 and HOXB3.

目的 观察术前肠内免疫营养对食管癌新辅助化疗患者营养状态、免疫状况及临床结局的影响.方法 选取行食管癌切除手术的患者65例,按随机表分为肠内免疫营养组(EIN组,34例)和常规饮食组(对照组,31例).所有入组患者术前均行新辅助化疗2周期,并于新辅助化疗结束后3～4周行食管癌根治术.EIN组于新辅助化疗第2疗程结束后1周开始在常规饮食基础上口服肠内免疫营养,直至术前1d.对照组于新辅助化疗第2疗程结束后只给予常规饮食.观察2组患者新辅助化疗第2疗程结束后1周及术前1d的体质量指数、肱三头肌皮皱厚度和上臂围.观察2组患者新辅助化疗第2疗程结束后1周、术前1d、术后1d、术后1周的营养及免疫指标.观察2组患者术后1d下床活动时间完成例数、术后首次肛门排气时间、术后肠内营养相关不良反应发生例数、术后肺炎发生例数和住院时间.结果 2组患者在性别、年龄、吸烟史、饮酒史、临床分期、肿瘤位置等方面比较差异无统计学意义(P>0.05).术前1 d EIN组的体质量指数、肱三头肌皮皱厚度和上臂围与对照组相比差异有统计学意义(均P<0.05).术前1 d EIN组营养指标和免疫指标显著上升(P<0.05);术后1 d 2组各营养指标和免疫指标均明显下降,与术前1 d相比差异有统计学意义(P<0.05);术后1周2组患者各指标较术后1 d显著上升(P<0.05).术后1周2组指标和免疫指标相比差异有统计学意义(P<0.05).术后下床活动完成例数EIN组较对照组明显增多,术后肠内营养相关不良反应(腹胀、腹泻)及肺炎并发症例数EIN组较对照组少,术后首次排气时间和住院时间EIN组比对照组均较短,差异有统计学意义(P<0.05).结论 对于食管癌新辅助化疗患者,术前口服肠内免疫营养,能改善患者的营养状态和免疫状况,增加患者对手术的耐受力,降低并发症的发生,促进患者的快速康复.

BACKGROUND Non-small cell lung cancer (NSCLC) is one of the most common human malignancies and the leading cause of cancer-related death. Over the past few decades, genomic alterations of cancer driver genes have been identified in NSCLC, and molecular testing and targeted therapies have become standard care for lung cancer patients. Here we studied the unique genomic profile of driver genes in Chinese patients with NSCLC by next-generation sequencing (NGS) assay. MATERIALS AND METHODS A total of 1,200 Chinese patients with NSCLC were enrolled in this study. The median age was 60 years (range: 26-89), and 83% cases were adenocarcinoma. NGS-based genomic profiling of major lung cancer-related genes was performed on formalin-fixed paraffin-embedded tumor samples and matched blood. RESULTS Approximately 73.9% of patients with NSCLC harbored at least one actionable alteration recommended by the National Comprehensive Cancer Network guideline, including epidermal growth factor receptor (EGFR), ALK, ERBB2, MET, BRAF, RET, and ROS1. Twenty-seven patients (2.2%) harbored inherited germline mutations of cancer susceptibility genes. The frequencies of EGFR genomic alterations (both mutations and amplification) and ALK rearrangement were identified as 50.1% and 7.8% in Chinese NSCLC populations, respectively, and significantly higher than the Western population. Fifty-six distinct uncommon EGFR mutations other than L858R, exon19del, exon20ins, or T790M were identified in 18.9% of patients with EGFR-mutant NSCLC. About 7.4% of patients harbored both sensitizing and uncommon mutations, and 11.6% of patients harbored only uncommon EGFR mutations. The uncommon EGFR mutations more frequently combined with the genomic alterations of ALK, CDKN2A, NTRK3, TSC2, and KRAS. In patients <40 years of age, the ALK-positive percentage was up to 28.2%. Moreover, 3.2% of ALK-positive patients harbored multi ALK rearrangements, and seven new partner genes were identified. CONCLUSION More unique features of cancer driver genes in Chinese NSCLC were identified by next-generation sequencing. These findings highlighted that NGS technology is more feasible and necessary than other molecular testing methods, and suggested that the special strategies are needed for drug development and targeted therapy for Chinese patients with NSCLC. IMPLICATIONS FOR PRACTICE Molecular targeted therapy is now the standard first-line treatment for patients with advanced non-small cell lung cancer (NSCLC). Samples of 1,200 Chinese patients with NSCLC were analyzed through next-generation sequencing to characterize the unique feature of uncommon EGFR mutations and ALK fusion. The results showed that 7.4% of EGFR-mutant patients harbored both sensitizing and uncommon mutations and 11.6% harbored only uncommon mutations. Uncommon EGFR mutations more frequently combined with the genomic alterations of ALK, CDKN2A, NTRK3, TSC2, and KRAS. ALK fusion was more common in younger patients, and the frequency decreased monotonically with age. 3.2% of ALK-positive patients harbored multi ALK rearrangement, and seven new partner genes were identified.

Esophageal squamous cell carcinoma (ESCC) is the predominant form with the highest incidence. We aimed to find metastasis-related differentially expressed long noncoding RNAs (lncRNAs), microRNAs (miRNAs), and messenger RNA (mRNAs) in ESCC. We first obtained the lncRNAs, miRNAs, and mRNAs profiles. The differentially expressed lncRNAs, miRNAs, and mRNAs were obtained, followed by the functional annotation. Then the interaction networks of miRNA-mRNA, lncRNA-mRNA coexpression, lncRNA-miRNA, and lncRNA-miRNA-mRNA were constructed. In addition, systematic expression pattern analysis of differentially expressed lncRNAs, miRNA, and mRNA in the normal, metastasis, and nonmetastasis was performed. Survivability of differentially expressed lncRNAs, miRNAs, and mRNA was analyzed. A total of 613 differentially expressed lncRNAs, 35 differentially expressed miRNAs, and 1586 differentially expressed mRNAs were obtained. Several interactions of H19-hsa-mir-222-chromobox 2 (CBX2), H19-hsa-mir-330-phosphoinositide-3-kinase regulatory subunit 4 (PIK3R4), KCNQ1 opposite strand/antisense transcript 1 (KCNQ1OT1)/CTB-89H12.4-hsa-mir-374a-vascular endothelial growth factor A (VEGFA), MALAT1/X inactive specific transcript (XIST)/XIST antisense RNA (TSIX)-hsa-mir-340-tumor necrosis factor receptor superfamily member 10A (NFRSF10A) were identified to play key roles in the metastasis of ESCC. In addition, KCNQ1OT1, TSIX, and XIST were significantly associated with the survival time of patients. In conclusion, our study may be helpful in understanding the pathological mechanism and providing new diagnostic and therapeutic biomarkers for ESCC.