Comparative efficacy of different combinations of acapella, active cycle of breathing technique, and external diaphragmatic pacing in perioperative patients with lung cancer: a randomised controlled trial.

BACKGROUND: Acapella plus active cycle of breathing technique (ACBT), external diaphragm pacemaker (EDP) plus ACBT have been shown to facilitate the recovery of functional capacity and lung function in patients suffering from airway obstruction but the efficacy in perioperative patients with lung cancer has not been proven. METHODS: We conducted a three-arm, prospective, randomized, assessor-blinded, controlled trial in patients with lung cancer who underwent thoracoscopic lobectomy or segmentectomy in the department of thoracic surgery, China. Patients were randomly assigned (1:1:1) to receive Acapella plus ACBT, EDP plus ACBT, or ACBT group (control group) using SAS software. The primary outcome was functional capacity, measured by the 6-minute walk test (6MWT). RESULTS: We recruited 363 participants over 17 months: 123 assigned to the Acapella plus ACBT group, 119 to the EDP plus ACBT group, and 121 to the ACBT group. Statistically significant differences were noted for functional capacity between the EDP plus ACBT and control groups at each follow-up time (1-week follow-up: difference = 47.25 m, 95% CI, 31.56-62.93; P < 0.001; and 1-month follow-up: difference = 49.72 m, 95% CI, 34.04-65.41; P < 0.001), between the Acapella plus ACBT and control groups at postoperative week 1 (difference = 35.23 m, 95% CI, 19.30-51.16; P < 0.001) and postoperative month 1 (difference = 34.96 m, 95% CI, 19.03-50.89; P < 0.001), and between the EDP plus ACBT and Acapella plus ACBT groups at 1-month follow-up (difference = 14.76 m, 95% CI, 1.34-28.19; P = 0.0316). CONCLUSION: EDP plus ACBT and Acapella plus ACBT significantly improved functional capacity and lung function in perioperative patients with lung cancer, compared with single-model ACBT, and the effects of EDP plus ACBT were clearly superior to those of other programs. TRIAL REGISTRATION: The study was registered in the clinical trial database (clinicaltrials.gov) on June 4, 2021 (No. NCT04914624).

Efficacy and safety of esophagectomy via left thoracic approach versus via right thoracic approach for middle and lower thoracic esophageal cancer: a multicenter randomized clinical trial (NST1501).

Background: Left thoracic approach (LTA) has been a favorable selection in surgical treatment for esophageal cancer (EC) patients in China before minimally invasive esophagectomy (MIE) is popular. This study aimed to demonstrate whether right thoracic approach (RTA) is superior to LTA in the surgical treatment of middle and lower thoracic esophageal squamous cell carcinoma (TESCC). Methods: Superiority clinical trial design was used for this multicenter randomized controlled two-parallel group study. Between April 2015 and December 2018, cT1b-3N0-1M0 TESCC patients from 14 centers were recruited and randomized by a central stratified block randomization program into LTA or RTA groups. All enrolled patients were followed up every three months after surgery. The software SPSS 20.0 and R 3.6.2. were used for statistical analysis. Efficacy and safety outcomes, 3-year overall survival (OS) and disease-free survival (DFS) were calculated and compared using the Kaplan-Meier method and the log-rank test. Results: A total of 861 patients without suspected upper mediastinal lymph nodes (umLN) were finally enrolled in the study after 95 ineligible patients were excluded. 833 cases (98.7%) were successfully followed up until June 1, 2020. Esophagectomies were performed via LTA in 453 cases, and via RTA in 408 cases. Compared with the LTA group, the RTA group required longer operating time (274.48±78.92 vs. 205.34±51.47 min, P<0.001); had more complications (33.8% vs. 26.3% P=0.016); harvested more lymph nodes (LNs) (23.61±10.09 vs. 21.92±10.26, P=0.015); achieved a significantly improved OS in stage IIIa patients (67.8% vs. 51.8%, P=0.022). The 3-year OS and DFS were 68.7% and 64.3% in LTA arm versus 71.3% and 63.7% in RTA arm (P=0.20; P=0.96). Conclusions: Esophagectomies via both LTA and RTA can achieve similar outcomes in middle or lower TESCC patients without suspected umLN. RTA is superior to LTA and recommended for the surgical treatment of more advanced stage TESCC due to more complete lymphadenectomy. Trial Registration: ClinicalTrials.gov NCT02448979.

Active cycle of breathing technique may reduce pulmonary complications after esophagectomy: A randomized clinical trial.

BACKGROUND: The purpose of the study was to determine whether the active cycle of breathing technique (ACBT) has an impact on postoperative pulmonary complication (PPC) after esophagectomy. METHODS: In this prospective randomized trial, patients who were candidates for esophagectomy were randomized into groups, wherein they received either ACBT (n = 146) or conventional chest physiotherapy (control group, n = 145) on postoperative days (POD) 1-3. The primary outcome was PPC. The secondary outcomes included the incidence of anastomotic leakage (AL), efficacy of airway clearance, and postoperative hospital length of stay (LOS). RESULTS: After esophagectomy, the PPC rate was significantly lower in the ACBT group (15.2%) than in the control group (31.0%) (p = 0.001). The incidences of AL were 5.5% and 12.4% in the ACBT and control groups, respectively (p = 0.042). Mean hospital LOS was 12.3 days for the ACBT group and 16.8 days for the control group (p = 0.008). ACBT significantly increased the mean sputum wet weight (g) on POD 1-3 when compared with conventional therapy (POD 1 9.08 vs. 6.47, POD 2 16.86 vs. 10.92, POD 3 24.65 vs. 13.52, all p < 0.001). Multivariable analysis revealed that ACBT decreased the rates of PPC (odds ratio [OR] 0.403, p = 0.003), AL (OR 0.379，p = 0.038)，arrhythmia (OR 0.397, p = 0.028), and bronchoscopy aspiration (OR 0.362, p = 0.016). CONCLUSION: ACBT is an effective airway clearance technique that significantly reduces the incidence of PPC after esophagectomy. ACBT could also significantly reduce both AL and LOS.

An Approach to Accelerate Healing and Shorten the Hospital Stay of Patients With Anastomotic Leakage After Esophagectomy: An Explorative Study of Systematic Endoscopic Intervention.

OBJECTIVE: To explore the comprehensive role of systemic endoscopic intervention in healing esophageal anastomotic leak. METHODS: In total, 3919 consecutive patients with esophageal cancer who underwent esophagectomy and immediate esophageal reconstruction were screened. In total, 203 patients (5.10%) diagnosed with anastomotic leakage were included. The participants were divided into three groups according to differences in diagnosis and treatment procedures. Ninety-four patients received conventional management, 87 patients received endoscopic diagnosis only, and the remaining 22 patients received systematic endoscopic intervention. The primary endpoint was overall healing of the leak after oncologic esophageal surgery. The secondary endpoints were the time from surgery to recovery and the occurrence of adverse events. RESULTS: 173 (85.2%; 95% CI, 80.3-90.1%) of the 203 patients were successfully healed, with a mean healing time of 66.04 ± 3.59 days (median: 51 days; range: 13-368 days), and the overall healing rates differed significantly among the three groups according to the stratified log-rank test (P<0.001). The median healing time of leakage was 37 days (95% CI: 33.32-40.68 days) in the endoscopic intervention group, 51 days (95% CI: 44.86-57.14 days) in the endoscopic diagnostic group, and 67 days (95% CI: 56.27-77.73 days) in the conventional group. The overall survival rate was 78.7% (95% CI: 70.3 to 87.2%) in the conventional management group, 89.7% (95% CI: 83.1 to 96.2%) in the endoscopic diagnostic group and 95.5% (95% CI: 86.0 to 100%) in the systematic endoscopic intervention group. Landmark analysis indicated that the speed of wound healing in the endoscopic intervention group was 2-4 times faster at any period than that in the conservative group. There were 20 (21.28%) deaths among the 94 patients in the conventional group, 9 (10.34%) deaths among the 87 patients in the endoscopic diagnostic group and 1 (4.55%) death among the 22 patients in the endoscopic intervention group; this difference was statistically significant (Fisher exact test, P < 0.05). CONCLUSION: Tailored endoscopic treatment for postoperative esophageal anastomotic leakage based on endoscopic diagnosis is feasible and effective. Systematic endoscopic intervention shortened the treatment period and reduced mortality and should therefore be considered in the management of this disease.

Modification of Pathologic T Classification for Non-small Cell Lung Cancer With Visceral Pleural Invasion: Data From 1,055 Cases of Cancers ≤ 3 cm.

BACKGROUND: Visceral pleural invasion (VPI) with PL1 or PL2 increases the T classification from T1 to T2 in non-small cell lung cancers (NSCLCs) ≤ 3 cm. We proposed a modified T classification based on VPI to guide adjuvant therapy. RESEARCH QUESTION: Is it reasonable to upstage PL1-positive cases from T1 to T2 for NSCLCs ≤ 3 cm? STUDY DESIGN AND METHODS: In total, 1,055 patients with resected NSCLC were retrospectively included. Tumor sections were restained with hematoxylin and eosin stain and Victoria blue elastic stain for the elastic layer. Disease-free survival (DFS) and overall survival (OS) were calculated by the Kaplan-Meier method. Subgroup analysis and a Cox proportional hazards model were used to further determine the impact of VPI on survival. RESULTS: The extent of VPI was diagnosed as PL0 in 824 patients, PL1 in 133 patients, and PL2 in 98 patients. The 5-year DFS rates of patients with PL0, PL1, and PL2 were 62.6%, 60.2%, and 28.8% (P < .01), whereas the corresponding 5-year OS rates were 78.6%, 74.4%, and 50.0% (P < .01), respectively. As predicted, the DFS and OS of patients with PL2 were much worse than those of patients with PL0 (P < .01) and PL1 (P < .01). However, both the DFS and OS of patients with PL0 and PL1 were comparable (DFS: P = .198; OS: P = .150). For node-negative cases, the DFS and OS of patients with PL0 and PL1 were also comparable (DFS: P = .468; OS: P = .388), but patients with PL2 had much worse DFS and OS than patients with PL0 (P < .01) and PL1 (P < .01). Multivariable analyses suggested that PL2, together with node positivity and poor cell differentiation, was an independent adverse prognostic factor. INTERPRETATION: In NSCLCs ≤ 3 cm, tumors with PL1 should remain defined as T1, not T2. Overtreatment by adjuvant chemotherapy in node-negative NSCLCs ≤ 3 cm might be avoided in PL1 cases.

Prognostic Value of a Four-miRNA Signature in Patients With Lymph Node Positive Locoregional Esophageal Squamous Cell Carcinoma Undergoing Complete Surgical Resection.

OBJECTIVE: This study was intended to identify prognostic biomarkers for lymph node (LN)-positive locoregional esophageal squamous cell carcinoma (ESCC) patients. SUMMARY OF BACKGROUND DATA: Surgery is a major treatment for LN-positive locoregional ESCC patients in China. However, patient outcomes are poor and heterogeneous. METHODS: ESCC-associated miRNAs were identified by microarray and validated by quantitative real-time polymerase chain reaction analyses in ESCC and normal esophageal epithelial samples. A multi-miRNA based classifier was established using a least absolute shrinkage and selection operator model in a training set of 145 LN-positive locoregional ESCCs, and further assessed in internal testing and independent validation sets of 145 and 243 patients, respectively. RESULTS: Twenty ESCC-associated miRNAs were identified and validated. A 4-miRNA based classifier (miR-135b-5p, miR-139-5p, miR-29c-5p, and miR-338-3p) was generated to classify LN-positive locoregional ESCC patients into high and low-risk groups. Patients with high-risk scores in the training set had a lower 5-year overall survival rate [8.7%, 95% confidence interval (CI): 0-20.3] than those with low-risk scores (50.3%, 95% CI: 40.0-60.7; P < 0.0001). The prognostic accuracy of the classifier was validated in the internal testing (P < 0.0001) and independent validation sets (P = 0.00073). Multivariate survival analyses showed that the 4-miRNA based classifier was an independent prognostic factor, and the combination of the 4-miRNA based classifier and clinicopathological prognostic factors significantly improved the prognostic accuracy of clinicopathological prognostic factors alone. CONCLUSION: Our 4-miRNA based classifier is a reliable prognostic prediction tool for overall survival in LN-positive locoregional ESCC patients and might offer a novel probability of ESCC treatment individualization.

Endobronchial Ultrasound Improves Evaluation of Recurrent Laryngeal Nerve Lymph Nodes in Esophageal Squamous Cell Carcinoma Patients.

BACKGROUND: The bilateral recurrent laryngeal nerve (RLN) lymph nodes are the most common metastatic site for esophageal squamous cell carcinoma (ESCC); however, the RLNs are susceptible to injury during dissection. Clinically, there is an urgent need to determine an effective diagnostic method for RLN nodes to help achieve selective nodal dissection and avoid potential serious complications by performing more conservative surgery for those with nonmetastatic nodes. Here, we innovatively applied endobronchial ultrasonography (EBUS) and investigated its diagnostic performance for preoperative evaluation of RLN nodes in ESCC patients. PATIENTS AND METHODS: All 81 enrolled ESCC patients underwent preoperative EBUS and CT examinations. The ability of EBUS and CT to detect RLN node metastasis was evaluated based on the resulting sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV). RESULTS: The diagnostic performance of EBUS was superior to that of CT; in particular, EBUS of the left RLN (L-RLN) nodes presented the best sensitivity, specificity, PPV, NPV, and accuracy compared with EBUS evaluations of the right RLN (R-RLN) nodes, CT of the L-RLN and R-RLN nodes. Moreover, EBUS combined with CT increased the NPV relative to that of EBUS or CT alone, promoting the ability to identify true-negative RLN nodes. In particular, the NPVs of the combined modality were 100% for both the L- and R-RLN nodes in early-T-stage (T1-T2) ESCC. CONCLUSIONS: EBUS is an efficient tool for RLN node evaluation, and the combination with CT may provide better guidance for selective RLN node dissection in ESCC patients.

The Study of Tumor Volume as a Prognostic Factor in T Staging System for Non-Small Cell Lung Cancer: An Exploratory Study.

BACKGROUND: This study aimed to evaluate T staging system for non-small cell lung cancer (NSCLC) using tumor volume (TV) and other prognostic factors. METHODS: This study included 1309 cases. The TV and greatest tumor diameter (GTD) were semi-automatically measured. The receiver operating characteristic (ROC) curves of TV and GTD were used to predict survival. The regression analysis was used to describe the correlation between GTD and TV. Overall survival (OS) was analyzed using the Kaplan-Meier method. Cox's proportional hazards regression model was applied for multivariate analysis. RESULTS: Using the OS in pN0M0 patients (997 cases), we obtained 4 optimal cutoff values and divided all cases into 5 TV groups (V1: TV ≤ 2.80 cm3; V2: TV > 2.80-6.40 cm3; V3: TV > 6.40-12.9 cm3; V4: TV > 12.9-55.01 cm3; V5: TV > 55.01 cm3) with significant OS (P < 0.001). Multivariate analysis showed that age, visceral pleural invasion (VPI), and all TV cutoff points were independent factors of OS (P < 0.05). For V3 and V4 groups, the OS in patients without VPI was better than that in patients with VPI. Using the values of TV, VPI, and N stages, we classified all cases into 5 stages from I to V depending on the OS. The OS in I, II, III, IV, and V stages were 71.3%, 65.5%, 59.8%, 47.7%, and 35.1% respectively (P < 0.001). CONCLUSIONS: We proposed a new T staging system using TV as the main prognostic descriptor in NSCLC patients, which may provide a better comprehensive clinical value than GTD in clinical applications.

Tumor volume is more reliable to predict nodal metastasis in non-small cell lung cancer of 3.0 cm or less in the greatest tumor diameter.

BACKGROUND: In this study, we sought to evaluate the correlation between TV, GTD, and lymph node metastases in NSCLC patients with tumors of GTD ≤ 3.0 cm. METHODS: We retrospectively analyzed the characteristics of clinicopathologic variables for lymph node involvement in 285 NSCLC patients with tumors of GTD ≤ 3.0 cm who accepted curative surgical resection. The TVs were semi-automatically measured by a software, and optimal cutoff points were obtained using the X-tile software. The relationship between GTD and TV were described using non-linear regression. The correlation between GTD, TV, and N stages was analyzed using the Pearson correlation coefficient. The one-way ANOVA was used to compare the GTD and TV of different lymph node stage groups. RESULTS: The relationship between GTD and TV accorded with the exponential growth model: y = 0.113e1.455x (y = TV, x = GTD). TV for patients with node metastases (4.78 cm3) was significantly greater than those without metastases (3.57 cm3) (P < 0.001). However, there were no obvious GTD differences in cases with or without lymph node metastases (P = 0.054). We divided all cases into three TV groups using the two cutoff values (0.9 cm3 and 3.9 cm3), and there was an obvious difference in the lymphatic involvement rate between the groups (P < 0.001). The tendency to metastasize was greater with higher TV especially when the TV was > 0.9-14.2 cm3 (P = 0.010). CONCLUSIONS: For NSCLC tumors with GTD ≤ 3.0 cm, TV is a more sensitive marker than GTD in predicting the positive lymph node metastases. The likelihood for metastasis increases with an increasing TV especially when GTD is > 2.0-3.0 cm.

Impact of L4 lymph node dissection on long-term survival in left-side operable non-small-cell lung cancer: a propensity score matching study.

OBJECTIVES: We investigated the impact of level 4 (L4) lymph node dissection (LND) on overall survival (OS) in left-side resectable non-small-cell lung cancer (NSCLC), with the aim of guiding lymphadenectomy. METHODS: A total of 1929 patients with left-side NSCLC who underwent R0 resection between 2001 and 2014 were included in the study. The patients were divided into a group with L4 LND (L4 LND+) and a group without L4 LND (L4 LND-). Propensity score matching was applied to minimize selection bias. The Kaplan-Meier method and Cox proportional hazards model were used to assess the impact of L4 LND on OS. RESULTS: A total of 317 pairs were matched. Of the cohort of patients, 20.3% (391/1929) had L4 LND. Of these patients, 11.8% (46/391) presented with L4 lymph node metastasis. L4 lymph node metastasis was not associated with the primary tumour lobes (P = 0.61). Before propensity score matching, the 5-year OS was comparable between the L4 LND+ and L4 LND- groups (69.0% vs 65.2%, P = 0.091). However, after propensity score matching, the 5-year OS of the L4 LND+ group was much improved compared to that of the L4 LND- group (72.9% vs 62.3%, P = 0.002) and L4 LND was an independent factor favouring OS (hazard ratio 0.678, 95% confidence interval 0.513-0.897; P = 0.006). Subgroup analysis suggested that L4 LND was an independent factor favouring OS in left upper lobe tumours. CONCLUSIONS: In patients with left-side operable NSCLC, L4 lymph node metastasis was not rare and L4 LND should be routinely performed.

Preoperative serum C-reactive protein levels and postoperative survival in patients with esophageal squamous cell carcinoma: a propensity score matching analysis.

OBJECTIVES: This study tested the relationship between preoperative serum C-reactive protein (CRP) levels and cancer-specific prognosis in patients with esophageal squamous cell carcinoma who have undergone curative resection. METHODS: We conducted a retrospective study on 961 patients with esophageal squamous cell cancer who underwent curative esophagectomy from 2006 to 2012 at the Sun Yat-sen University Cancer Center. Preoperative serum CRP levels were determined, and a cutoff value of 5.0 mg/mL was established. Propensity score matching (PSM) was performed to reduce the selection bias between patients with low CRP (≤ 5.0 mg/mL) and those with high CRP (> 5.0 mg/mL) levels based on age, tumor-lymph node-metastasis (TNM) stage, and tumor grade. The prognostic value of preoperative CRP levels was determined using life table, Kaplan-Meier, and Cox proportional hazards analyzes. RESULTS: In the unmatched cohort, the 3-year and 5-year survival rates were 57 and 53%, respectively, in patients with high preoperative CRP levels (> 5.0 mg/mL) and 68 and 56%, respectively, in those with low preoperative CRP levels (≤ 5.0 mg/mL). The difference in the survival rates of the 2 groups was significant (p = 0.004). Univariate survival analysis revealed that the preoperative CRP levels, TNM stage, tumor grade, drinking history, and anastomosis method were prognostic factors for overall survival (OS). Before conducting PSM, the low-CRP group had a lower age (p = 0.001), lower histological grade (p = 0.086), and lower TNM stage (p = 0.254). After PSM, 176 patients with low CRP levels and 176 of those with high CRP levels were enrolled in the analysis. In the matched cohort, the 3-year and 5-year survival rates were 56 and 50%, respectively, in patients with high preoperative CRP levels (> 5.0 mg/mL) and 68 and 56%, respectively, in those with low preoperative CRP levels (≤ 5.0 mg/mL). The difference in the survival rates between the low- and high-CRP groups was significant (p = 0.044). Multivariate analysis of the matched patients revealed that the TNM stage and preoperative CRP level were independent prognostic factors for OS. CONCLUSIONS: A high preoperative CRP level (> 5.0 mg/mL) predicts worse survival prognosis in patients who have undergone curative resection for esophageal squamous cell cancer.

Tumor Volume Is Better Than Diameter for Predicting the Prognosis of Patients with Early-Stage Non-small Cell Lung Cancer.

BACKGROUND: This study aimed to investigate whether tumor volume (TV) is better than diameter for predicting the prognosis of patients with early-stage non-small cell lung cancer (NSCLC) after complete resection. METHODS: This study retrospectively reviewed the clinicopathologic characteristics of 274 patients with early-stage NSCLC who had received pretreatment computed tomography (CT) scans and complete resection. TV was semi-automatically measured from CT scans using an imaging software program. The optimal cutoff of TV was determined by X-tile software. Disease-free survival (DFS) and overall survival (OS) were assessed by the Kaplan-Meier method. The prognostic significance of TV and other variables was assessed by Cox proportional hazards regression analysis. RESULTS: Using 3.046 cm3 and 8.078 cm3 as optimal cutoff values of TV, the patients were separated into three groups. A larger TV was significantly associated with poor DFS and OS in the multivariable analysis. Kaplan-Meier curves of DFS and OS showed significant differences on the basis of TV among patients with stage 1a disease, greatest tumor diameter (GTD) of 2 cm or smaller, and GTD of 2-3 cm, respectively. Using two TV cutoff points, three categories of TV were created. In 54 cases (19.7%), patients migrated from the GTD categories of 2 cm or smaller, 2-3 cm, and larger than 3 cm into the TV categories of 3.046 cm3 or smaller, 3.046-8.078 cm3, and larger than 8.078 cm3. CONCLUSION: TV is an independent prognostic factor of DFS and OS for early-stage NSCLC. The findings show that TV is better than GTD for predicting the prognosis of patients with early-stage NSCLC.

The incidence and distribution of mediastinal lymph node metastasis and its impact on survival in patients with non-small-cell lung cancers 3 cm or less: data from 2292 cases.

OBJECTIVES: Our goal was to investigate the incidence and distribution of mediastinal lymph node metastases (MLNM) in non-small-cell lung cancers (NSCLC) 3 cm or less, with the purpose of guiding mediastinal lymph node dissection. METHODS: A total of 2292 cases seen between January 2001 and December 2014 were included. These patients were grouped according to the lobes with the primary tumours. The incidence and distribution of pathological MLNM were compared among the groups. The impact of MLNM on overall survival was also compared. RESULTS: The most common mediastinal metastatic sites for different primary tumour lobes were as follows: right upper lobe, 17.7% (87/492) for level 4R; right middle lobe, 14.9% (28/188) for level 7; right lower lobe, 19.8% (82/414) for level 7; left upper lobe, 18.2% (96/528) for level 5; and left lower lobe, 16.6% (42/253) for level 7. For patients with tumours in the upper lobe, the median survival time was 32 months for those with MLNM in the subcarinal zone or lower zone compared with 83 months for those with MLNM only in the upper zone (P < 0.01). When the tumours were 1 cm or less, the incidence of MLNM to the lower zone for upper lobe tumours and of MLNM to the upper zone for lower lobe tumours was zero. CONCLUSIONS: Different primary NSCLC lobe locations have a different propensity to be sites of MLNM for those tumours that are 3 cm or less. For tumours no larger than 1 cm, a lower zone mediastinal lymph node dissection might be unnecessary for upper lobe tumours and an upper zone mediastinal lymph node dissection might be unnecessary for lower lobe tumours.

Adjuvant radiotherapy, chemotherapy or surgery alone for high-risk histological node negative esophageal squamous cell carcinoma: Protocol for a multicenter prospective randomized controlled trial.

Histologically node negative esophageal squamous cell carcinoma (pN0 ESCC) after radical resection still carries a significant risk of recurrence, especially in high-risk patients. Our previous study showed that the risk of recurrence was associated with tumor location and cell differentiation, as well as the presence of lymphovascular invasion. Most recurrence occurs within two years after surgery. There is still a lack of knowledge on the risks or potential benefits of postoperative adjuvant therapies for high-risk pN0 ESCC patients. This study was designed to evaluate the efficacy and toxicity of adjuvant therapies after radical surgery in high-risk patients with pN0 ESCC. This study is a multicenter, prospective, controlled randomized trial, which will compare the differences between either adjuvant chemotherapy or adjuvant radiotherapy and surgery alone for high-risk pN0 ESCC. Patients in group A will receive three cycles of adjuvant chemotherapy with paclitaxel and cisplatin, patients in group B will receive adjuvant radiotherapy with intensity-modulated radiation of 50 Gy, and patients in group C (the control) will receive surgery alone. The primary endpoint is three-year disease-free survival. Secondary endpoints include toxicity of adjuvant therapies and five-year overall survival. One hundred and sixty-two patients in each group are required and a total of 486 patients will finally be enrolled into the study. This will be the first randomized trial to investigate the necessity or potential benefit of postoperative adjuvant therapies for high-risk pN0 ESCC patients.

Incidence and Distribution of Lobe-Specific Mediastinal Lymph Node Metastasis in Non-small Cell Lung Cancer: Data from 4511 Resected Cases.

OBJECTIVE: We aimed to investigate the incidence and distribution of mediastinal lymph node metastases (MLNM) in operable non-small cell lung cancer (NSCLC) with the purpose of guiding mediastinal lymph node dissection (MLND). METHODS: A total of 4511 NSCLC patients who underwent resection between January 2001 and December 2014 were included. These patients were preoperatively untreated and grouped according to the primary tumor lobes. The incidence and distribution of pathologic MLNM were compared among groups, and multivariate analysis was conducted to find the independent factors impacting MLNM. RESULTS: Lymph node involvement was observed in 1784 patients (39.5%). A total of 628 cases (13.9%) were N1-positive only, 752 cases (16.7%) were both N1- and N2-positive, and 404 cases (9.0%) were N2-positive only. The most common sites of mediastinal metastasis for different primary tumor lobes were the right upper lobe, station 4R (21.5%, 192/893); right middle lobe, station 7 (21.1%, 69/327); right lower lobe, station 7 (24.1%, 212/878); left upper lobe, station 5 (22.2%, 224/1008); and left lower lobe, station 7 (21.7%, 136/628). However, when only N2 cases were considered, each mediastinal lymph node zone can be involved with metastasis to a high proportion (> 5%). Multivariable analyses showed that poor cell differentiation, adenocarcinoma, larger tumor size, central type, and younger age were independent factors favoring MLNM. CONCLUSIONS: Different primary tumor locations have a different propensity to be sites of MLNM; however, once MLNM occurs, each zone can be involved and should not be neglected. Systematic MLND is the preferred procedure for operable NSCLC.

Thoracoscopic Surgery Versus Thoracotomy for Lung Cancer: Short-Term Outcomes of a Randomized Trial.

BACKGROUND: Safety and short-term efficacy of video-assisted thoracoscopic surgery (VATS) for early-stage non-small lung cancer (NSCLC) has been demonstrated by observational studies previously. However, these outcomes have never been verified by a large randomized controlled trial (RCT). The aim of our RCT was to confirm that VATS is not inferior or even superior to open operation for early-stage NSCLC in terms of short-term and oncologic efficacy. METHODS: The trial was undertaken at five tertiary hospitals. Patients aged between 18 and 75 years with clinically early-stage NSCLC were randomly assigned to the VATS and axillary thoracotomy groups. Lobectomy plus mediastinal lymph node dissection was standard surgical intervention. Because patients continue to be followed up for oncologic outcome, the short-term perioperative outcomes would be reported here. RESULTS: Between 2008 and 2014, 508 patients were recruited and 425 were eligible for analyses (215 VATS and 210 axillary thoracotomy). Eight VATS procedures were converted to open operation intraoperatively (3.72%). Median operation time with VATS was significantly less than axillary thoracotomy (150 versus 166 minutes, p = 0.009). In addition, VATS was associated with less intraoperative blood loss (p = 0.001). There was no difference for postoperative pleural drainage, length of hospitalization, and rates of morbidity and mortality. Cancer residual margins were found in 1 patient with VATS and 5 with axillary thoracotomy (p = 0.128). The yield of lymph nodes from either surgical approach was similar (p = 0.389). CONCLUSIONS: Our study demonstrates that VATS lobectomy is safe and reliable to treat NSCLCs, and it may be superior to axillary thoracotomy for operation time and intraoperative blood loss. ClinicalTrials.gov identifier: NCT01102517.

Entinostat reverses cisplatin resistance in esophageal squamous cell carcinoma via down-regulation of multidrug resistance gene 1.

Cisplatin resistance frequently occurs in esophageal squamous cell carcinoma (ESCC). The underlying mechanism for cisplatin resistance in ESCC remains largely obscure. Here we report that entinostat reversed cisplatin resistance in ESCC both in vitro and in vivo by induction of apoptosis and inhibition of cell proliferation, accompanied by a decrease of multidrug resistance gene 1 (MDR1), P-Src, Mcl-1, Cyclin D1 and an increase of cleaved PARP. MDR1 expression was associated with worsen survival of ESCC patients with cisplatin-based chemotherapy. Dasatinib potentiated entinostat to overcome cisplatin resistance. By inhibiting Src, dasatinib reduced the expression of MDR1 and Mcl-1. Furthermore, Obatoclax, an inhibitor of Mcl-1, obviously decreased the expression of MDR1, suggesting that entinostat might surmount cisplatin resistance in ESCC via a Src-Mcl-1-MDR1 pathway. Interestingly, cisplatin also enhanced the effect of entinostat both in vitro and in vivo. Our data disclose a molecular basis that entinostat reverses cisplatin resistance, and provide a promising strategy with combinatorial drugs to treat cisplatin resistant ESCC patients.

Tumor-stroma ratio (TSR) in non-small cell lung cancer (NSCLC) patients after lung resection is a prognostic factor for survival.

BACKGROUND: In recent years, the tumor-stroma ratio (TSR) has been considered to a new and independent predictive variable for the prognosis of some kinds of neoplasms. The objective of this study was to assess the prognostic significance of the TSR in non-small cell lung cancer (NSCLC). METHODS: A cohort of 261 NSCLC patients who underwent radical surgery of lung cancer were included in the present study. Two independent observers visually estimated the TSR on hematoxylin-eosin (H&E) stained tissue pathological slices. According to the proportion of stroma ≥50% or <50%, We separate the patients into two groups: those with stroma-poor and those with stroma-rich tumors. RESULTS: Both univariate and multivariate analyses disclosed that the TSR was associated with overall survival (OS) [hazard ratio (HR), 1.741; 95% confidence intervals (CI), 1.040-2.913 and HR, 1.904; 95% CI, 1.132-3.202, respectively]. The HR values for disease-free survival (DFS) were 1.795 (95% CI, 1.073-3.005) and 2.034 (95% CI, 1.210-3.420). The OS and DFS of patients with stroma-poor tumors were better than those with stroma-rich tumors. CONCLUSIONS: These results demonstrated that the TSR is a new prognostic factor for NSCLC. Stroma-poor tumors were associated with longer disease-free period and better prognosis than were stroma-rich tumors in NSCLC patients. The TSR may contribute to the development of individualized treatment for NSCLC in the future.