Analysis of the Trends and Influencing Factors for Postoperative Cough in Patients with Esophageal Cancer Based on Patient-Reported Outcomes.

BACKGROUND: Cough is a common symptom that affects patients' recovery and quality of life after esophagectomy. This study sought to investigate trends in postoperative cough and the factors that influence cough. METHODS: A total of 208 of 225 patients were enrolled in this study. The Mandarin Chinese version of the Leicester Cough Questionnaire was administered the day before surgery and at three time points (1 week, 1 month, and 3 months) after esophagectomy to assess patient-reported outcomes. RESULTS: All patients' LCQ-MC scores after surgery were lower than presurgery (P < 0.05), with the lowest score found 1 week after esophagectomy. Factors associated with a cough 1 week after surgery included clinical stage of cancer (OR 0.782, 95% CI 0.647-0.944, P = 0.011), anastomotic position (OR 1.241, 95% CI 1.069-1.441, P = 0.005), duration of surgery (OR 0.759, 95% CI 0.577-0.998, P = 0.049), and subcarinal lymph node dissection (OR 0.682, 95% CI 0.563-0.825, P < 0.001). Factors associated with a cough one month after surgery included clinical stage (OR 0.782, 95% CI 0.650-0.940, P = 0.009), anastomotic position (OR 1.293, 95% CI 1.113-1.503, P = 0.001), and maintaining a semi-reclining position (OR 1.440, 95% CI 1.175-1.766, P < 0.001). Factors associated with a cough 3 months after surgery were clinical stage (OR 0.741, 95% CI 0.591-0.928, P = 0.009) and anastomotic position (OR 1.220, 95% CI 1.037-1.435, P = 0.016). CONCLUSIONS: This study showed that the factors influencing postoperative cough differed over time following esophagectomy. These results may warrant prospective intervention to better manage patients undergoing surgery for esophageal cancer to prevent postoperative cough.

Carbon emissions and priming effects derived from crop residues and their responses to nitrogen inputs.

Crop residue-derived carbon (C) emissions and priming effects (PE) in cropland soils can influence the global C cycle. However, their corresponding generality, driving factors, and responses to nitrogen (N) inputs are poorly understood. As a result, the total C emissions and net C balance also remain mysterious. To address the above knowledge gaps, a meta-analysis of 1123 observations, taken from 51 studies world-wide, has been completed. The results showed that within 360 days, emission ratios of crop residues C (ER) ranged from 0.22% to 61.80%, and crop residues generally induced positive PE (+71.76%). Comparatively, the contribution of crop residue-derived C emissions (52.82%) to total C emissions was generally higher than that of PE (12.08%), emphasizing the importance of reducing ER. The ER and PE differed among crop types, and both were low in the case of rice, which was attributed to its saturated water conditions. The ER and PE also varied with soil properties, as PE decreased with increasing C addition ratio in soils where soil organic carbon (SOC) was less than 10‰; in contrast, the opposite phenomenon was observed in soils with SOC exceeding 10‰. Moreover, N inputs increased ER and PE by 8.31% and 3.78%, respectively, which was predominantly attributed to (NH4 )2 SO4 . The increased PE was verified to be dominated by microbial stoichiometric decomposition. In summary, after incorporating crop residues, the total C emissions and relative net C balance in the cropland soils ranged from 0.03 to 23.47 mg C g-1 soil and 0.21 to 0.97 mg C g-1 residue-C g-1 soil, respectively, suggesting a significant impact on C cycle. These results clarify the value of incorporating crop residues into croplands to regulate global SOC dynamics and help to establish while managing site-specific crop return systems that facilitate C sequestration.

Seasonal and Spatial Fluctuations of Reactive Oxygen Species in Riparian Soils and Their Contributions on Organic Carbon Mineralization.

Reactive oxygen species (ROS) are ubiquitous in the natural environment and play a pivotal role in biogeochemical processes. However, the spatiotemporal distribution and production mechanisms of ROS in riparian soil remain unknown. Herein, we performed uninterrupted monitoring to investigate the variation of ROS at different soil sites of the Weihe River riparian zone throughout the year. Fluorescence imaging and quantitative analysis clearly showed the production and spatiotemporal variation of ROS in riparian soils. The concentration of superoxide (O2•-) was 300% higher in summer and autumn compared to that in other seasons, while the highest concentrations of 539.7 and 20.12 µmol kg-1 were observed in winter for hydrogen peroxide (H2O2) and hydroxyl radicals (•OH), respectively. Spatially, ROS production in riparian soils gradually decreased along with the stream. The results of the structural equation and random forest model indicated that meteorological conditions and soil physicochemical properties were primary drivers mediating the seasonal and spatial variations in ROS production, respectively. The generated •OH significantly induced the abiotic mineralization of organic carbon, contributing to 17.5-26.4% of CO2 efflux. The obtained information highlighted riparian zones as pervasive yet previously underestimated hotspots for ROS production, which may have non-negligible implications for carbon turnover and other elemental cycles in riparian soils.

Comparing a PD-L1 inhibitor plus chemotherapy to chemotherapy alone in neoadjuvant therapy for locally advanced ESCC: a randomized Phase II clinical trial : A randomized clinical trial of neoadjuvant therapy for ESCC.

BACKGROUND: A Phase II study was undertaken to evaluate the safety and efficacy of the neoadjuvant socazolimab, a novel PD-L1 inhibitor, in combination with nab-paclitaxel and cisplatin for locally advanced esophageal squamous cell carcinoma (ESCC). METHODS: Sixty-four patients were randomly divided between the Socazolimab + nab-paclitaxel + cisplatin (TP) arm (n = 32) and the control arm (n = 32), receiving either socazolimab (5 mg/kg intravenously (IV), day 1) or a placebo with nab-paclitaxel (125 mg/m2 IV, day 1/8) and cisplatin (75 mg/m2 IV, day 1) repeated every 21 days for four cycles before surgery. The primary endpoint was major pathological response (MPR), and the secondary endpoints were pathological complete response (pCR), R0 resection rate, event-free survival (EFS), overall survival (OS), and safety. RESULTS: A total of 29 (90.6%) patients in each arm underwent surgery, and 29 (100%) and 28 (98.6%) patients underwent R0 resection in the Socazolimab + TP and Placebo + TP arms, respectively. The MPR rates were 69.0 and 62.1% (95% Confidence Interval (CI): 49.1-84.0% vs. 42.4-78.7%, P = 0.509), and the pCR rates were 41.4 and 27.6% (95% CI: 24.1-60.9% vs. 13.5-47.5%, P = 0.311) in the Socazolimab + TP and Placebo + TP arms, respectively. Significantly higher incidence rates of ypT0 (37.9% vs. 3.5%; P = 0.001) and T downstaging were observed in the Socazolimab + TP arm than in the Placebo + TP arm. The EFS and OS outcomes were not mature. CONCLUSIONS: The neoadjuvant socazolimab combined with chemotherapy demonstrated promising MPR and pCR rates and significant T downstaging in locally advanced ESCC without increasing surgical complication rates. TRIAL REGISTRATION: Registration name (on clinicaltrials.gov): A Study of Anti-PD-L1 Antibody in Neoadjuvant Chemotherapy of Esophageal Squamous Cell Carcinoma. REGISTRATION NUMBER: NCT04460066.

Biochar-Associated Free Radicals Reduce Soil Bacterial Diversity: New Insight into Ecoenzymatic Stoichiometry.

The toxicity of environmentally persistent free radicals (EPFRs), often generated during biochar production, on soil bacteria is still not truly reflected when considering the conditions in real soil. Herein, the influence of free radicals within biochar on soil bacteria was investigated from the perspectives of enzyme activity, community structure, and ecoenzymatic stoichiometry. Biochar addition enhanced the contents of EPFRs and derived hydroxyl radicals (•OH) in the soil, while it reduced bacterial alpha diversity by 5.06-35.44%. The results of redundancy analysis and inhibition experiments collectively demonstrated the key role of EPFRs and •OH in reducing the bacterial alpha diversity. Specifically, EPFRs and •OH increased the stoichiometric imbalance by promoting the release of dissolved organic carbon and ammonium N, thus aggravating the P limitation in soil. This was further confirmed by increased alkaline phosphatase activity from 702 to 874 nmol g-1 h-1. The P limitation induced by EPFRs and •OH decreased the bacterial alpha diversity, as evidenced by the negative correlation between P limitation and bacterial alpha diversity (r2 = -0.931 to -0.979, P < 0.01) and the structural equation model. The obtained results demonstrate a ubiquitous but previously overlooked mechanism for bacterial toxicity of biochar-associated free radicals, providing scientific guidance for safe utilization of biochar.

Mapping of Lymph Node Metastasis From Thoracic Esophageal Cancer: A Retrospective Study.

OBJECTIVES: This retrospective study was designed to investigate the optimal extent of dissection for thoracic esophageal cancer (EC) based on the incidence of lymph node metastasis (LNM). METHODS: We retrospectively identified 1014 patients with thoracic esophageal carcinoma who underwent esophagectomy at our institution between May 2018 and November 2020. Also, the location and rate of LNM in relation to the postoperative pathological results were retrieved. We separately counted the metastasis rates of routinely excised lymph node stations according to the Japan Esophageal Society (JES) staging system. RESULTS: A total of 1666 consecutive patients were screened, and 1014 were enrolled. Generally, the rates of LNM in thoracic EC may be arranged in the descending order of station 7 > station 106recR > station 2 > station 106recL. Esophageal cancer in the middle and lower thoracic segment also had a high rate of LNM along bilateral recurrent laryngeal nerve. Stations 106tbL and 111 were the lowest frequent sites of metastasis with rate less than 5%; only the patients with clinically positive LNs need to dissect. The cT3-4, cN+, or G3 were independent risk factors for LNM and neoadjuvant therapy did not change the distribution of LNM for thoracic EC cases. CONCLUSIONS: This study accurately identified the distribution of LNM for thoracic EC patients. Neoadjuvant therapy could not change the overall distribution of LNM in thoracic EC patients. However, whether LNs dissection at stations 106tbL and 111 is related to the survival of thoracic EC or not, needs a long follow-up time to verify.

The prognostic significance of the circumferential resection margin in esophageal squamous cell carcinoma patients without neoadjuvant treatment.

BACKGROUND: Circumferential resection margin (CRM) is very important in esophageal cancer, but its diagnostic criteria has not been unified. The College of American Pathologists (CAP) and the Royal College of Pathologists (RCP) provide two different criteria. The aim of this study is to evaluate the long-term prognostic significance of CRM status with different CRM criteria in esophageal squamous cell carcinoma (ESCC). METHODS: Influence of CRM status according to the CAP and RCP criteria on long-term survival of 838 patients with resected pT3 tumors and without neoadjuvant therapy was analyzed. Patients stratified into three groups on the basis of tumor distance from the CRM (CRM > 1 mm, 0-1 mm, and 0 mm) were also analysed. RESULTS: Positive CRM was found in 59 (7%) patients according to the CAP criteria and 317 (37.8%) patients according to the RCP criteria. Univariate and multivariate survival analysis showed that CRM status, according to three different criteria, was independent prognostic factor. However, subgroup analysis showed that the prognostic value of CRM status was limited to certain metastatic lymph node load. In pN0 subgroup, patients with CRM > 1 mm had better prognosis than patients with CRM 0-1 mm. Patients with CRM 0 mm had worse outcome than patients with CRM > 0 mm in pN1-2 subgroup. But CRM status had no prognosis value in pN3 subgroup. CONCLUSIONS: The CRM status is an important prognostic factor in ESCC patients, but this effect was limited to patients without or with less lymph node metastasis (pN0-2). In clinical practice, we recommend the 1 mm-three-tier criteria as it provides more prognostic value than the traditional two-tier criteria.

Quantitative RECIST derived from multiparametric MRI in evaluating response of esophageal squamous cell carcinoma to neoadjuvant therapy.

OBJECTIVE: To develop a quantitative Response Evaluation Criteria in Solid Tumors (qRECIST) for evaluating response to neoadjuvant therapy (nT) in ESCCs relying on multiparametric (mp) MRI. METHODS: Patients with cT2-T4a/N0-N3/M0 ESCC undergoing pre-nT and post-nT esophageal mpMRI before radical resection were prospectively included. Images were reviewed by two experienced radiologists. qRECIST was redefined using four methods including conventional criterion (cRECIST) and three model-dependent RECIST relying on quantitative MRI measurements at pre-nT, post-nT, and delta pre-post nT, respectively. Pathological tumor regression grades (TRGs) were used as a reference standard. The rates of agreement between four qRECIST methods and TRGs were determined with a Cronbach's alpha test, area under the curve (AUC), and a diagnostic odds ratio meta-analysis. RESULTS: Ninety-one patients were enrolled. All four methods revealed high inter-reader agreements between the two radiologists, with a Kappa coefficient of 0.96, 0.87, 0.88, and 0.97 for cRECIST, pre-nT RECIST, post-nT RECIST, and delta RECIST, respectively. Among them, delta RECIST achieved the highest overall agreement rate (67.0% [61/91]) with TRGs, followed by post-nT RECIST (63.8% [58/91]), cRECIST (61.5% [56/91]), and pre-nT RECIST (36.3% [33/91]). Especially, delta RECIST achieved the highest accuracy (97.8% [89/91]) in distinguishing responders from non-responders, with 97.3% (34/35) for responders and 98.2% (55/56) for non-responders. Post-nT RECIST achieved the highest accuracy (93.4% [85/91]) in distinguishing complete responders from non-pCRs, with 77.8% (11/18) for pCRs and 94.5% (69/73) for non-pCRs. CONCLUSION: The qRECIST with mpMRI can assess treatment-induced changes and may be used for early prediction of response to nT in ESCC patients. KEY POINTS: • Quantitative mpMRI can reliably assess tumor response, and delta RECIST model had the best performance in evaluating response to nT in ESCCs, with an AUC of 0.98, 0.95, 0.80, and 0.82 for predicting TRG0, TRG1, TRG2, and TRG3, respectively. • In distinguishing responders from non-responders, the rate of agreement between delta RECIST and pathology was 97.3% (34/35) for responders and 98.2% (55/56) for non-responders, resulting in an overall agreement rate of 97.8% (89/91). • In distinguishing pCRs from non-pCR, the rate of agreement between MRI and pathology was 77.8% (11/18) for pCRs and 94.5% (69/73) for non- pCRs, resulting in an overall agreement rate of 91.2% (83/91).

Recycling of heavy metals and modification of biochar derived from Napier grass using HNO3.

The disposal of biomass enriched with heavy metals (HMs) limits the application of phytoextraction. This study investigated the feasibility of obtaining K-rich fertilizer with low risk of HMs and biochar with good application prospect by extracting Napier grass biochar using 15% HNO3 and separating HMs from the filtrate using 40% KOH. In this study, Napier grass biochar produced at 500 °C showed better potential for utilization owing to its relatively low HM contents, high nutrient contents, and high yield. In fact, 61.26% Cd, 84.22% Zn, and more K were extracted from biochar when the pH was adjusted to 1 using 15% HNO3. Then, Cd and Zn could be almost separated from the filtrate by adjusting the pH to 10 or more by adding 40% KOH. The Cd content in the biochar was reduced from a low risk level to a no-risk level, and the Zn content in the biochar was reduced from a medium risk level to a low risk level when the pH was adjusted to 1 and 2 by adding 15% HNO3. The adsorption capacity of biochar to dyes was enhanced when the pH was adjusted to 1 using 15% HNO3. The cation exchange mechanism endows the biochar with better potential for reuse (for methylene blue). This work provides a safe, efficient, and maneuverable resource allocation method.

CircRNA CircZMYM4 inhibits the growth and metastasis of lung adenocarcinoma via the miR-587/ODAM pathway.

Circular RNAs (circRNAs) are known to regulate tumorigenesis. In this study, circRNAs microarray was used to analyze the circRNA expression in lung adenocarcinoma (LUAD) tissues, and CircRNA zinc finger MYM-type containing 4(circZMYM4) was selected for further analysis. In this study, we detected circZMYM4 expression in LUAD specimens and cell lines using RT-PCR. The expression of circZMYM4 was further verified in the GEO datasets and TCGA datasets. Gain-of-function and loss-of-function experiments were used to analyze the effects of circZMYM4 on LUAD in vivo and in vitro. The relationship between miR-587 and circZMYM4 or ODAM was predicted by bioinformatics tools and confirmed using dual-luciferase reporter assays and RNA-pull down. We found that circZMYM4 was distinctly down-regulated in LUAD tissues and cell lines. Functional assays revealed that circZMYM4 overexpression suppressed LUAD cell proliferation, metastasis and suppressed apoptosis, while miR-587 overexpression could weaken these effects. Importantly, circZMYM4 upregulated ODAM expression via sponging miR-587 to suppress LUAD progression. ODAM knockdown could reverse the repressive effect of circZMYM4 overexpression on cell proliferation, migration and invasion abilities. Overall, circZMYM4 regulates the miR-587/ODAM axis to suppress LUAD progression, which may become a potential biomarker and therapeutic target.

The value of intravoxel incoherent motion diffusion-weighted imaging in predicting the pathologic response to neoadjuvant chemotherapy in locally advanced esophageal squamous cell carcinoma.

OBJECTIVE: To explore the value of intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) for the prediction of pathologic response to neoadjuvant chemotherapy (NAC) in locally advanced esophageal squamous cell carcinoma (ESCC). MATERIAL AND METHODS: Forty patients with locally advanced ESCC who were treated with NAC followed by radical resection were prospectively enrolled from September 2015 to May 2018. MRI and IVIM were performed within 1 week before and 2-3 weeks after NAC, prior to surgery. Parameters including apparent diffusion coefficient (ADC), true diffusion coefficient (D), pseudodiffusion coefficient (D*), and pseudodiffusion fraction (f) before and after NAC were measured. Pathologic response was evaluated according to the AJCC tumor regression grade (TRG) system. The changes in IVIM values before and after therapy in different TRG groups were assessed. Receiver operating characteristic (ROC) curves analysis was used to determine the best cutoff value for predicting the pathologic response to NAC. RESULTS: Twenty-two patients were identified as TRG 2 (responders), and eighteen as TRG 3 (non-responders) in pathologic evaluation. The ADC, D, and f values increased significantly after NAC. The post-NAC D and ΔD values of responders were significantly higher than those of non-responders. The area under the curve (AUC) was 0.722 for post-NAC D and 0.859 for ΔD in predicting pathologic response. The cutoff values of post-NAC D and ΔD were 1.685 × 10-3 mm2/s and 0.350 × 10-3 mm2/s, respectively. CONCLUSION: IVIM-DWI may be used as an effective functional imaging technique to predict pathologic response to NAC in locally advanced ESCC. KEY POINTS: • The optimal cutoff values of post-NAC D and ΔD for predicting pathologic response to NAC in locally advanced ESCC were 1.685 × 10-3 mm2/s and 0.350 × 10-3 mm2/s, respectively. • Pathologic response to NAC in locally advanced ESCC was favorable in patients with post-NAC D and ΔD values that were higher than the optimal cutoff values. • IVIM-DWI can potentially be used to preoperatively predict pathologic response to NAC in esophageal carcinoma. Accurate quantification of the D value derived from IVIM-DWI may eventually translate into an effective and non-invasive marker to predict therapeutic efficacy.

MRI features in differentiating mucosal high-grade neoplasia from early invasive squamous cell cancer of the esophagus.

OBJECTIVES: To evaluate the diagnostic accuracy of unenhanced and contrast-enhanced MRI in the differentiation of mucosal high-grade neoplasia (MHN) from early invasive squamous cell cancer (EISCC) of the esophagus. METHODS: Between March 2015 and January 2019, 72 study participants with MHN (n = 46) and EISCC (n = 26) of the esophagus were enrolled in this prospective study. Postoperative histopathologic analysis was the reference standard. All participants underwent MRI (T2-multi-shot turbo spin-echo sequence (msTSE), diffusion-weighted imaging (DWI), and 3D gradient-echo-based sequence (3D-GRE)). Two radiologists, blinded to participants' data, independently evaluated MRI and assigned MR features including shape (mucosal thickening or focal mass), signal on T2-msTSE and DWI, enhancement degree (intense or slight), and enhancement pattern (homogeneous, heterogeneous, or heart-shaped). Diagnostic performance of the 5 features was compared using the chi-square test; kappa values were assessed for reader performance. RESULTS: Surgery was performed within 3.6 + 3.5 days after MR imaging. Inter-reader agreement on MR features was excellent (kappa value = 0.854, p < 0.001). All 8 mass-like MHN were "heart-shaped" in appearance. The degree of enhancement showed the best diagnosis performance in differentiating between MHN and EISCC of the esophagus. The combination of all 5 features had only borderline improved sensitivity, specificity, and AUC of 100%, 96.2%, and 0.999, respectively, which was not statistically significant compared with the degree of enhancement alone. CONCLUSIONS: MRI can differentiate MHN from EISCC in esophagus; the presence of "heart-shaped" appearance favors the diagnosis of MHN. KEY POINTS: • All 8 mass-like MHN showed a "heart-shaped" enhancement pattern which may help differentiating MHN from EISCC. • Degree of enhancement had the best diagnostic performance in differentiating between MHN and EISCC in esophagus. • The combined 5 features (shape, signal in T2-msTSE and DWI, enhancement degree, and enhancement pattern) provided sensitivity, specificity, and AUC of 100%, 96.2%, and 0.999, respectively, which was not statistically significant than tumor enhancement alone in distinguishing MHN from EISCC.

The value of GRASP on DCE-MRI for assessing response to neoadjuvant chemotherapy in patients with esophageal cancer.

BACKGROUND: To compare the value of two dynamic contrast-enhanced Magnetic Resonance Images (DCE-MRI) reconstruction approaches, namely golden-angle radial sparse parallel (GRASP) and view-sharing with golden-angle radial profile (VS-GR) reconstruction, and evaluate their values in assessing response to neoadjuvant chemotherapy (nCT) in patients with esophageal cancer (EC). METHODS: EC patients receiving nCT before surgery were enrolled prospectively. DCE-MRI scanning was performed after nCT and within 1 week before surgery. Tumor Regression Grade (TRG) was used for chemotherapy response evaluation, and patients were stratified into a responsive group (TRG1 + 2) and a non-responsive group (TRG3 + 4 + 5). Wilcoxon test was utilized for comparing GRASP and VS-GR reconstruction, Kruskal-Wallis and Mann-Whitney test was performed for each parameter to assess response, and Spearman test was performed for analyzing correlation between parameters and TRGs, as well as responder and non-responder. The receiver operating characteristic (ROC) was utilized for each significant parameter to assess its accuracy between responders and non-responders. RESULTS: Among the 64 patients included in this cohort (52 male, 12 female; average age of 59.1 ± 7.9 years), 4 patients showed TRG1, 4 patients were TRG2, 7 patients were TRG3, 11 patients were TRG4, and 38 patients were TRG5. They were stratified into 8 responders and 56 non-responders. A total of 15 parameters were calculated from each tumor. With VS-GR, 10/15 parameters significantly correlated with TRG and response groups. Of these, only AUCmax showed moderate correlation with TRG, 7 showed low correlation and 2 showed negligible correlation with TRG. 8 showed low correlation and 2 showed negligible correlation with response groups. With GRASP, 13/15 parameters significantly correlated with TRG and response groups. Of these, 10 showed low correlation and 3 showed negligible correlation with TRG. 11 showed low correlation and 2 showed negligible correlation with TRG. Seven parameters (AUC* > 0.70, P < 0.05) showed good performance in response groups. CONCLUSIONS: In patients with esophageal cancer on neoadjuvant chemotherapy, several parameters can differentiate responders from non-responders, using both GRASP and VS-GR techniques. GRASP may be able to better differentiate these two groups compared to VS-GR. Trial registration for this prospective study: ChiCTR, ChiCTR-DOD-14005308. Registered 2 October 2014.

The MR radiomic signature can predict preoperative lymph node metastasis in patients with esophageal cancer.

PURPOSE: To assess the role of the MR radiomic signature in preoperative prediction of lymph node (LN) metastasis in patients with esophageal cancer (EC). PATIENTS AND METHODS: A total of 181 EC patients were enrolled in this study between April 2015 and September 2017. Their LN metastases were pathologically confirmed. The first half of this cohort (90 patients) was set as the training cohort, and the second half (91 patients) was set as the validation cohort. A total of 1578 radiomic features were extracted from MR images (T2-TSE-BLADE and contrast-enhanced StarVIBE). The lasso and elastic net regression model was exploited for dimension reduction and selection of the feature space. The multivariable logistic regression analysis was adopted to identify the radiomic signature of pathologically involved LNs. The discriminating performance was assessed with the area under receiver-operating characteristic curve (AUC). The Mann-Whitney U test was adopted for testing the potential correlation of the radiomic signature and the LN status in both training and validation cohorts. RESULTS: Nine radiomic features were selected to create the radiomic signature significantly associated with LN metastasis (p < 0.001). AUC of radiomic signature performance in the training cohort was 0.821 (95% CI: 0.7042-0.9376) and in the validation cohort was 0.762 (95% CI: 0.7127-0.812). This model showed good discrimination between metastatic and non-metastatic lymph nodes. CONCLUSION: The present study showed MRI radiomic features that could potentially predict metastatic LN involvement in the preoperative evaluation of EC patients. KEY POINTS: • The role of MRI in preoperative staging of esophageal cancer patients is increasing. • MRI radiomic features showed the ability to predict LN metastasis in EC patients. • ICCs showed excellent interreader agreement of the extracted MR features.

Accuracy of 3-T MRI for Preoperative T Staging of Esophageal Cancer After Neoadjuvant Chemotherapy, With Histopathologic Correlation.

OBJECTIVE: The purpose of this study was to explore the value of 3-T MRI for evaluating the preoperative T staging of esophageal cancer (EC) treated with neoadjuvant chemotherapy (NAC), with histopathologic confirmation. SUBJECTS AND METHODS: This prospective study enrolled patients for whom endoscopic biopsy showed EC and pretreatment CT showed stage cT1N+M0 or cT2-T4aN0-N3M0. All patients received two cycles of NAC (paclitaxel and nedaplatin protocol) followed by 3-T MRI and surgical resection. Readers assigned a T category on MRI, and postoperative pathologic confirmation was considered the reference standard. Interreader agreement, the diagnostic accuracy of T staging on T2-weighted turbo spin-echo (TSE) BLADE (Siemens Healthcare), contrast-enhanced StarVIBE (Siemens Healthcare), high-resolution delayed phase StarVIBE, and the combination of the three sequences were analyzed and compared with postoperative pathologic T staging. RESULTS: The study included 79 patients. Mean time between NAC and MRI was 23 days. Interreader agreements of T category assignment were excellent for T2-weighted TSE BLADE (κ = 0.810, p < 0.0001), contrast-enhanced StarVIBE (κ = 0.845, p < 0.0001), high-resolution delayed phase StarVIBE (κ = 0.897, p < 0.0001), and the combination of the three sequences (κ = 0.880, p < 0.0001). The highest accuracy for T0, T1, T2, and T4a lesions was on high-resolution delayed phase StarVIBE (96.2%, 92.4%, 91.1%, and 91.1% for reader 1; 94.9%, 89.9%, 91.1%, and 94.9% for reader 2), and the highest accuracy for T3 lesions was on T2-weighted TSE BLADE (92.4% and 94.9% for reader 1 and reader 2, respectively). Diagnostic accuracy of the combination of the three sequences was not improved compared with individual sequences. CONCLUSION: High-resolution delayed phase StarVIBE had the highest diagnostic accuracy in staging EC after NAC for all T categories except T3, for which T2-weighted TSE BLADE had the highest accuracy. Combining all three sequences did not improve diagnostic accuracy.

Comparison of neoadjuvant chemoradiotherapy and neoadjuvant chemotherapy for esophageal cancer: a meta-analysis.

Aim: To compare the clinical efficacy of neoadjuvant chemoradiotherapy (nCRT) and neoadjuvant chemotherapy (nCT) for esophageal cancer. Methods: Randomized controlled trials reporting on the comparison of nCRT and nCT for esophageal cancer were identified. Results: Three eligible randomized controlled trials were identified and included with a total of 375 patients (189 nCRT, 186 nCT). Outcomes showed that compared with nCT group, R0 resection and pathologic complete response (pCR) rates were significantly increased in nCRT group. However, no significant difference was seen in 3- and 5-year progression-free survival or 3- and 5-year overall survival. Conclusion: The addition of radiotherapy to neoadjuvant chemotherapy results in higher R0 resection rate and pCR rate, without significantly impacting survival.

Comparison between free-breathing radial VIBE on 3-T MRI and endoscopic ultrasound for preoperative T staging of resectable oesophageal cancer, with histopathological correlation.

OBJECTIVES: To compare the T staging of resectable oesophageal cancer (OC) using radial VIBE (r-VIBE) and endoscopic ultrasound (EUS) with pathological confirmation of the T stage. METHODS: Forty-three patients with endoscopically proven OC and indeterminate T1/T2/T3/T4a stage by computed tomography (CT) and EUS were imaged on a 3-T magnetic resonance imaging (MRI) scanner. T stage was scored on MRI and EUS by two independent radiologists and one endoscopist, respectively, and compared with postoperative pathological findings. T staging agreement between r-VIBE and EUS with postoperative pathological T staging was analysed by a kappa test. RESULTS: EUS and pathological T staging showed agreement of 69.8% (30/43). Radial VIBE and pathological T staging agreement was 86.0% (37/43) and 90.7% (39/43) for readers 1 and 2, respectively. High accuracy for T1/T2 stage was obtained for both r-VIBE readers (90.5% and 100% for reader 1 and reader 2, respectively) and EUS reader (100%). For T3/T4, r-VIBE showed accuracy of 81.8% and 90.9% for reader 1 and reader 2, respectively, while for EUS, accuracy was only 68.2% compared with pathological T staging. CONCLUSIONS: Contrast-enhanced r-VIBE is comparable to EUS in T staging of resectable OC with stage of T1/T2, and is superior to EUS in staging of T3/T4 lesions. KEY POINTS: • Radial VIBE may be useful in preoperative T staging of OC • Accuracy of staging on r-VIBE is higher in T1/2 than in T3/4 • Accuracy of EUS was 100% and 68.2% for T1/T2 and T3/T4 stage • Inter-reader agreement of T staging for r-VIBE was good.

A systematic analysis of the resistance and sensitivity of HER2YVMA receptor tyrosine kinase mutant to tyrosine kinase inhibitors in HER2-positive lung cancer.

Human epidermal growth factor receptor 2 (HER2) has become a well-established target for the treatment of HER2-positive lung cancer. However, a frequently observed in-frame mutation that inserts amino acid quadruplex Tyr776-Val777-Met778-Ala779 at G776 (G776(YVMA)) in HER2 kinase domain can cause drug resistance and sensitivity, largely limiting the application of reversible tyrosine kinase inhibitors in lung cancer therapy. A systematic investigation of the intermolecular interactions between the HER2(YVMA) mutant and clinical small-molecule inhibitors would help to establish a complete picture of drug response to HER2 G776(YVMA) insertion in lung cancer, and to design new tyrosine kinase inhibitors with high potency and selectivity to target the lung cancer-related HER2(YVMA) mutant. Here, we combined homology modeling, ligand grafting, structure minimization, molecular simulation and binding affinity analysis to profile a number of tyrosine kinase inhibitors against the G776(YVMA) insertion in HER2. It is found that the insertion is far away from HER2 active pocket and thus cannot contact inhibitor ligand directly. However, the insertion is expected to induce marked allosteric effect on some regions around the pocket, including A-loop and hinges connecting between the N- and C-lobes of HER2 kinase domain, which may exert indirect influence to inhibitor binding. Most investigated inhibitors exhibit weak binding strength to both wild-type and mutant HER2, which can be attributed to steric hindrance that impairs ligand compatibility with HER2 active pocket. However, the cognate inhibitor lapatinib and the non-cognate inhibitor bosutinib were predicted to have low affinity for wild-type HER2 but high affinity for HER2(YVMA) mutant, which was confirmed by subsequent kinase assay experiments; the inhibitory potencies of bosutinib against wild-type and mutant HER2 were determined to be IC(50) > 1000 and =27 nM, respectively, suggesting that the bosutinib might be exploited as a selective inhibitor for mutant over wild-type HER2. Structural examination revealed that formation of additional non-bonded interactions such as hydrogen bonds and hydrophobic contacts with HER2 A-loop region due to G776(YVMA) insertion is the primary factor to improve bosutinib affinity upon the mutation.

Detorsion of the Pulmonary Torsion: A Rare Post-thoracotomy Complication.

Pulmonary torsion is a rare but serious condition. Without prompt treatment it progresses to lobar ischaemia, pulmonary infarction and finally fatal gangrene. We present a case of this rare complication in a 61-year-old woman following thoracic operation without involving any lung resection. Careful post-operative clinical observation, chest X-ray and CT scans are crucial for precise diagnosis of lobar torsion. The bedside radiograph provided initial evidence of torsion. Computed tomography scans revealed the presumptive diagnosis of right upper lobe torsion. On exploration, a 70° rotation of the right upper lobe in a clockwise direction was found. The lobar torsion was carefully relieved, and lobar fixation was performed as a prophylaxis against recurrence of this complication. The post-operative period was uneventful. Early recognition and prompt intervention is imperative in order to save the affected lung. Patients with well-developed interlobar fissures may benefit from pulmonary lobe fixation.