Multi-Omics Analysis Reveals the Role of Changes in Platelet Activation Pathways in the Survival Outcome of Patients with Esophageal Squamous Cell Carcinoma.

Objective: The objective of this study was to integrate metabolomics and transcriptomics data to identify key diagnostic and prognostic markers for esophageal squamous cell carcinoma (ESCC). Plasma samples were collected from 85 ESCC patients at different stages and 50 healthy volunteers for non-targeted metabolomic analysis. Methods: Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was employed for non-targeted metabolomic analysis. Subsequently, we integrated the metabolomic data with transcriptomic data from the Gene Expression Omnibus (GEO) and prognosis data from The Cancer Genome Atlas Program (TCGA) to perform pathway analysis. Our focus was on pathways that involve both metabolites and upstream genes, as they often exhibit higher accuracy. Results: Through the integration of metabolomics and transcriptomics, we identified significant alterations in the platelet activation pathway in ESCC. This pathway involves the participation of both metabolites and genes, making it a more accurate reflection of pathological changes associated with the disease. Notably, metabolite arachidonic acid (AA) and chemokine receptor type 2(CXCR2) were significantly downregulated in ESCC, while genes collagen type I alpha 1(COL1A1), collagen type I alpha 2(COL1A2), collagen type III alpha 1(COL3A1), type 3 inositol 1,4,5-trisphosphate receptor (ITPR3), and insulin-like growth factor II mRNA binding protein 3(IGF2BP3) were significantly upregulated, indicating the presence of tumor-induced platelet activation in ESCC. Further analysis of prognosis data revealed that high expression of COL1A1, IGF2BP3, and ITPR3 was associated with a favorable prognosis for ESCC, while high CXCR2 expression was linked to an adverse prognosis. In addition, we combined COL1A1, ITPR3, IGF2BP3, CXCR2, and AA to form a diagnostic biomarker panel. The receiver operating characteristic curve (ROC) demonstrated excellent diagnostic capability (AUC=0.987). Conclusion: Our study underscores the significant role of platelet activation pathways and related genes in the diagnosis and prognosis of ESCC patients. These findings offer promising insights for improving the clinical management of ESCC.

Pararespiratory and paradigestive lymph node metastases in esophageal squamous cell carcinoma: predicting survival and refining the N staging system.

BACKGROUND: The site of lymph node metastasis (LNM) may affect the prognosis of patients with esophageal squamous cell carcinoma (ESCC). To investigate the prognoses of pararespiratory and paradigestive LNM and to propose a novel N (nN) staging system that integrates both the LNM site and count. METHODS: This study was a multicenter, large-sample, retrospective cohort study that included ESCC patients with LNM between January 2014 and December 2019 from three Chinese institutes. Patients were set into training (two institutes) and external validation (one institute) cohorts. The primary outcomes were survival differences in LNM site and the development of novel nodal staging system. The overall survival (OS) of patients with pararespiratory LNM only (Group A), paradigestive LNM only (Group B), and both sites (Group C) was evaluated by Kaplan-Meier. Cox proportional hazards models were used to identify the independent prognostic factors. An nN staging system considering both the LNM site and count was developed and evaluated by the area under the receiver operating characteristic curve (AUC). RESULTS: In total, 1313 patients were included and split into training (n = 1033) and external validation (n = 280) cohorts. There were 342 (26.0%), 568 (43.3%) and 403 (30.7%) patients in groups A, B and C, respectively. The OS of patients with pararespiratory and patients with paradigestive LNM presented significant differences in the training and validation cohorts (P < 0.050). In the training cohort, LNM site was an independent prognostic factor (hazard ratio: 1.58, 95% confidence intervals: 1.41-1.77, P < 0.001). The nN staging definition: nN1 (1-2 positive pararespiratory/paradigestive LNs), nN2 (3-6 pararespiratory LNs or 1 pararespiratory with 1paradigestive LN), nN3 (3-6 LNs with ≥ 1 paradigestive LN), nN4 (≥ 7 LNs). Subsets of patients with different nN stages showed significant differences in OS (P < 0.050). The prognostic model of the nN staging system presented higher performance in the training and validation cohorts at 3-year OS (AUC, 0.725 and 0.751, respectively) and 5-year OS (AUC, 0.740 and 0.793, respectively) than the current N staging systems. CONCLUSIONS: Compared to pararespiratory LNM, the presence of paradigestive LNM is associated with worse OS. The nN staging system revealed superior prognostic ability than current N staging systems.

Double-lung versus heart-lung transplantation for end-stage cardiopulmonary disease: a systematic review and meta-analysis.

We compared posttransplant outcomes following double-lung transplantation (DLTx) and heart-lung transplantation (HLTx), based on a search of PubMed, Cochrane Library, and Embase, from inception to March 8, 2022, for studies that report outcomes of these procedures. We then performed a meta-analysis of baseline characteristics and posttransplant outcomes. Subgroup analyses were implemented according to indication, publication year, and center. This study was registered on PROSPERO (number CRD42020223493). Ten studies were included in this meta-analysis, involving 1230 DLTx patients and 1022 HLTx patients. The DLTx group was characterized by older donors (P = 0.04) and a longer allograft ischemia time (P < 0.001) than the HLTx group. The two groups had comparable 1-year, 3-year, 5-year, 10-year survival rates (all P > 0.05), with similar results identified in subgroup analyses. We found no significant differences in 1-year, 5-year, and 10-year chronic lung allograft dysfunction (CLAD)-free survival, length of intensive care unit stay and hospital stay, length of postoperative ventilation, in-hospital mortality, or surgical complications between the groups (all P > 0.05). Thus, DLTx provides similar posttransplant survival to HLTx for end-stage cardiopulmonary disease. These two procedures have a comparable risk of CLAD and other posttransplant outcomes.

A novel web-based dynamic nomogram for recurrent laryngeal nerve lymph node metastasis in esophageal squamous cell carcinoma.

Background: Patients with esophageal squamous cell carcinoma (ESCC) are liable to develop recurrent laryngeal nerve (RLN) lymph node metastasis (LNM). We aimed to assess the predictive value of the long diameter (LD) and short diameter (SD) of RLN lymph node (LN) and construct a web-based dynamic nomogram for RLN LNM prediction. Methods: We reviewed 186 ESCC patients who underwent RLN LN dissection from January 2016 to December 2018 in the Affiliated Hospital of North Sichuan Medical College. Risk factors for left and right RLN LNM were determined by univariate and multivariate analyses. A web-based dynamic nomogram was constructed by using logistic regression. The performance was assessed by the area under the curve (AUC) and Brier score. Models were internally validated by performing five-fold cross-validation. Results: Patients who underwent left and right RLN LN dissection were categorized as left cohort (n = 132) and right cohort (n = 159), with RLN LNM rates of 15.9% (21/132) and 21.4% (34/159), respectively. The AUCs of the LD (SD) of RLN LN were 0.663 (0.688) in the left cohort and 0.696 (0.705) in the right cohort. The multivariate analysis showed that age, the SD of RLN LN, and clinical T stage were significant risk factors for left RLN LNM (all P < 0.05), while tumor location, the SD of RLN LN, and clinical T stage were significant risk factors for right RLN LNM (all P < 0.05). The dynamic nomograms showed reliable performance after five-fold cross-validation [(left (right), mean AUC: 0.814, range: 0.614-0.891 (0.775, range: 0.084-0.126); mean Brier score: 0.103, range: 0.084-0.126 (0.145, range: 0.105-0.206)], available at https://mpthtw.shinyapps.io/leftnomo/ and https://mpthtw.shinyapps.io/rightnomo/. Conclusion: The LD and SD of RLN LN are inadequate to predict RLN LNM accurately, but online dynamic nomograms by combined risk factors show better prediction performance and convenient clinical application.

The minimum number of examined lymph nodes for accurate nodal staging and optimal survival of stage T1-2 esophageal squamous cell carcinoma: A retrospective multicenter cohort with SEER database validation.

BACKGROUND: The extent of lymphadenectomy during esophagectomy remains controversial for patients with T1-2 ESCC. The aim of this study was to identify the minimum number of examined lymph node (ELN) for accurate nodal staging and overall survival (OS) of patients with T1-2 esophageal squamous cell carcinoma (ESCC). MATERIALS AND METHODS: Patients with T1-2 ESCC from three institutes between January 2011 and December 2020 were retrospectively reviewed. The associations of ELN count with nodal migration and OS were evaluated using multivariable models, and visualized by using locally weighted scatterplot smoothing (LOWESS). Chow test was used to determine the structural breakpoints of ELN count. External validation in the SEER database was performed. RESULTS: In total, 1537 patients were included. Increased ELNs was associated with an increased likelihood of having positive nodal disease and incremental OS. The minimum numbers of ELNs for accurate nodal staging and optimal survival were 14 and 18 with validation in the SEER database (n = 519), respectively. The prognostic prediction ability of N stage was improved in the group with ≥14 ELNs compared with those with fewer ELNs (iAUC, 0.70 (95%CI 0.66-0.74) versus 0.61(95%CI 0.57-0.65)). The higher prognostic value was found for patients with ≥18 ELNs than those with <18 ELNs (iAUC, 0.78 (95%CI 0.74-0.82) versus 0.73 (95%CI 0.7-0.77)). CONCLUSION: The minimum numbers of ELNs for accurate nodal staging and optimal survival of stage T1-2 ESCC patients were 14 and 18, respectively.

Preoperative Clinical Characteristics Predict Recurrent Laryngeal Nerve Lymph Node Metastasis and Overall Survival in Esophageal Squamous Cell Carcinoma: A Retrospective Study With External Validation.

Background: Recurrent laryngeal nerve (RLN) lymph node metastasis (LNM) is not rare in patients with esophageal squamous cell carcinoma (ESCC). We aimed to develop and externally validate a preoperative nomogram using clinical characteristics to predict RLN LNM in patients with ESCC and evaluate its prognostic value. Methods: A total of 430 patients with ESCC who underwent esophagectomy with lymphadenectomy of RLN LNs at two centers between May 2015 and June 2019 were reviewed and divided into training (center 1, n = 283) and external validation cohorts (center 2, n = 147). Independent risk factors for RLN LNM were determined by multivariate logistic regression, and a nomogram was developed. The performance of the nomogram was assessed in terms of discrimination, calibration, clinical usefulness, and prognostic value. The nomogram was internally validated by the bootstrap method and externally validated by the external validation cohort. Results: Multivariate analysis indicated that clinical T stage (P <0.001), endoscopic tumor length (P = 0.003), bioptic tumor differentiation (P = 0.004), and preoperative carcinoembryonic antigen level (P = 0.001) were significantly associated with RLN LNM. The nomogram had good discrimination with the area under the curve of 0.770 and 0.832 after internal and external validations. The calibration curves and decision curve analysis confirmed the good calibration and clinical usefulness of this model. High-risk of RLN LNM predicted by the nomogram was associated with worse overall survival in the external validation cohort (P <0.001). Conclusion: A nomogram developed by preoperative clinical characteristics demonstrated a good performance to predict RLN LNM and prognosis for patients with ESCC.

Noninvasive methods for detection of chronic lung allograft dysfunction in lung transplantation.

Lung transplantation (LTx) is the only therapeutic option for end-stage lung diseases. Chronic lung allograft dysfunction (CLAD), which manifests as airflow restriction and/or obstruction, is the primary factor limiting the long-term survival of patients after surgery. According to histopathological and radiographic findings, CLAD comprises two phenotypes, bronchiolitis obliterans syndrome and restrictive allograft syndrome. Half of all lung recipients will develop CLAD in 5 years, and this rate may increase up to 75% 10 years after surgery owing to the paucity in accurate and effective early detection and treatment methods. Recently, many studies have presented noninvasive methods for detecting CLAD and improving diagnosis and intervention. However, the significance of accurately detecting CLAD remains controversial. We reviewed published studies that have presented noninvasive methods for detecting CLAD to highlight the current knowledge on clinical symptoms, spirometry, imaging examinations, and other methods to detect the disease.

Clinical nomogram for lymph node metastasis in pathological T1 esophageal squamous cell carcinoma: a multicenter retrospective study.

BACKGROUND: Endoscopic resection is increasingly used to treat pathological T1 (pT1) esophageal cancer (EC) patients. However, the procedures are limited by lymph node metastasis (LNM) and remain controversial. We aimed to construct a nomogram to predict the risk of LNM in patients with pT1 esophageal squamous cell carcinoma (ESCC). METHODS: A total of 243 patients with pT1 ESCC who underwent esophagectomy and lymph node dissection at two different institutes between February 2013 and June 2019 were analyzed retrospectively. Patients were categorized into the negative group and the positive group according to whether there was LNM. Risk factors for LNM were evaluated by univariate and multivariate analyses. The nomogram was used to estimate the individual risk of LNM. RESULTS: Forty-six (18.9%) of the 243 patients with pT1 ESCC exhibited LNM. The LNM rate in patients with stage T1a disease was 5.7% (5/88), and the rate in patients with stage T1b disease was 26.5% (41/155). Multivariable logistic regression analysis showed that tumor differentiation [odds ratio (OR) =1.942, 95% confidence interval (CI): 1.067-3.536, P=0.030], the T1 sub-stage (OR =4.750, 95% CI: 1.658-13.611, P=0.004), the preoperative alanine aminotransferase/aspartate aminotransferase ratio (LSR) (OR =5.371, 95% CI: 1.676-17.210, P=0.005), and the high-density lipoprotein cholesterol (HDL-C) level (OR =5.894, 95% CI: 1.917-18.124, P=0.002) were independent risk factors for LNM. The nomogram had relatively high accuracy, with an area under the receiver operating characteristic curve (AUC) of 0.803 (95% CI: 0.732-0.873). The calibration curve showed that the predicted probability of LNM was in good agreement with the actual probability. CONCLUSIONS: Clinicopathological and hematological parameters of tumor differentiation, the T1 sub-stage, the preoperative LSR, and the HDL-C level may predict the risk of LNM in T1 ESCC. The risk of LNM can be predicted by the nomogram.

Author Correction: Investigation of Dietary Factors and Esophageal Cancer Knowledge: Comparison of Rural Residents in High- and Low-incidence Areas.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.

Investigation of Dietary Factors and Esophageal Cancer Knowledge: Comparison of Rural Residents in High- and Low-incidence Areas.

To compare the differences in dietary status and knowledge of esophageal cancer (EC) between residents of high- and low-incidence areas. We investigated dietary conditions and EC knowledge among residents in high- and low-EC incidence areas (Yanting and Qingzhen counties). Residents in Yanting consumed more pickled vegetables, salted meat and barbecued food (P < 0.05). Analysis of the past ten-year trend in Yanting consumed fresh vegetables/fruits, beans, sauerkraut, hot food, and barbecued food had gradually increased, and the trend was less than that in Qingzhen County. However, the gradual increasing trend in consumption of pickled vegetables, pickled meat, and spicy food over the past 10 years was greater (P < 0.05). Drinking water in Yanting County was healthier than that in Qingzhen County (P < 0.05). In terms of EC knowledge, the proportions of residents in Yanting who had a clear understanding, knowledge or had heard of EC or knew the common causes, primary symptoms, therapeutic measures, preventive measures, and government interventions for EC were all higher than in Qingzhen (P < 0.05). Residents in Yanting had greater EC knowledge but more harmful dietary habits than those in Qingzhen.

Multiple intracranial metastases from postoperative giant sarcomatoid malignant pleural mesothelioma: A case report and literature review.

Sarcomatoid malignant pleural mesothelioma (SMPM) is a rare tumor with poor response to treatment and a dismal prognosis. Distant metastases are not uncommon and usually appear at the late stages of the disease. However, cerebral metastases have rarely been documented. We herein report a case of a giant sarcomatoid carcinoma of the pleura in a 41-year-old male patient with no history of exposure to asbestos, who presented with a chief complaint of left-sided chest pain for 1 month. Extrapleural pneumonectomy and rib excision were performed. At 5 months after the surgery, the patient was diagnosed with multiple intracranial metastatic neoplasms and succumbed to the disease soon thereafter. The aim of the present case report was to emphasize this rare metastatic pattern and aggressive clinical course of SMPM, with a supplementary review of the previously published literature.

Pulmonary chondroma: A clinicopathological study of 29 cases and a review of the literature.

The present retrospective study was designed to review the clinicopathological features and outcome of surgical treatment of pulmonary chondroma, and to accumulate data for the clinical diagnosis and therapy. The clinicopathological data from 29 patients, aged between 38- and 78-years-old, with pulmonary chondroma who underwent surgical operation between July 2003 and June 2015 were reviewed. Of these patients, 18 exhibited no clinical symptoms, 7 were characterized by coughing, hemoptysis, shortness of breath and other symptoms and only 3 patients exhibited chest pain as the predominant symptom. The average size of the neoplasms was 3.6 cm. All patients were pathologically diagnosed. Operative time was 126±22 min, the mean intraoperative blood loss was 82±23 ml and the drainage duration was 3.1±1.8 days. A total of 6 postoperative complications were noted. The patients were followed-up for 2-135 months. A total of 23 patients were alive without recurrence, 4 patients succumbed to mortality, 2 patients were lost at follow-up. Pulmonary chondroma is a rare benign tumor of the lung. The clinical symptoms were concealed and often misdiagnosed as a tuberculosis tumor, hamartoma, peripheral lung cancer or a single metastatic tumor. Complete resection was the best treatment providing patients with a good prognosis. After definite diagnosis, it is necessary to exclude Carney's triad.

Comparative study of self-expanding metal stent and intraluminal radioactive stent for inoperable esophageal squamous cell carcinoma.

BACKGROUND: We compared the effectiveness of self-expanding metal stent alone vs. radioactive stent embedded with 125I seeds implantation insertion in patients of inoperable esophageal squamous cell cancer combined with malignant esophageal stenosis. METHODS: We studied two groups of patients with stenosis attribute to inoperable esophageal squamous cell carcinoma. Group A had placed self-expanding metal stent alone insertion; group B encountered radioactive stent embedded with 125I seeds. Patients were followed up by monthly home visits or telephone interview. Survival time was analyzed with Kaplan-Meier analysis. Log rank test was used to analyze factors of survival time for all significant differences. RESULTS: There was no significant difference between the two groups of all baseline characteristics. There was no statistical difference in complications including massive hematemesis, pain more than 1 month, stent migration, and restenosis. Survival time and causes of death such as tumor metastasis, massive hemorrhage, non-tumor-related factors, and restenosis were comparable between the two groups (P>0.05). The medical costs were significantly less in group A than those in group B (P<0.01). CONCLUSIONS: Radioactive stent embedded with (125)I seeds was not significant in improving survival rate, but showed to increase hospitalization costs compared to self-expandable metal stent alone in treating inoperable esophageal squamous cell carcinoma stricture.

Fabrication of highly ordered/switchable polymer nanogratings for nano-actuators using nanoimprint lithography.

Polymer micro/nano-actuators are attracting tremendous interest due to their potential applications in micro/nano-mechanical systems and lab-on-a-chip systems. To achieve this, thin films of stimuli-responsive polymers are required to be patterned at the micro/nanometer scale, and also to possess highly ordered orientation in the responsive component. We demonstrate here that nanoscale patterning and uniaxial alignment of liquid crystalline mesogens can be simultaneously achieved by nanoimprint lithography performed in the liquid crystalline mesophase. Photoactive azobenzene mesogens were aligned parallel to the nanogratings imprinted in the films. The degree of alignment depended on the extent of nanoconfinement. The nanogratings expanded in the direction perpendicular to the film upon exposure to uniform UV irradiation, because of trans-to-cis isomerization. In addition, the reversible deformation amplitude strongly depended on the degree of alignment of the photoactive azobenzene mesogens.

[Clinical significance of cellular immune function in patients with viral myocarditis].

AIM: To probe into the clinical significance of cellular immune function in patients with viral myocarditis. METHODS: Choose our hospital in January 2008-December 2009 admitted during the 75 patients of viral myocarditis as the experimental group, 67 healthy patients served as control groups, respectively, and hospital admission within 24 h after the venous blood, before and after treatment T cell subsets, natural killer cells (NK) activity and tumor necrosis factor (TNF) were detected and analyzed. RESULTS: Compared with admission, 24 h after admission test in peripheral blood T lymphocyte subsets CD3, CD4, CD8 and CD4/CD8 were improved and CD3, CD4 and CD4/CD8 were statistically significant differences (P<0.05), but still slightly lower in the control group, while the difference was not statistically significant. At the same time, compared with admission, 24 h after admission of natural killer cells in the experimental group (NK) and tumor necrosis factor were improved, the differences were statistically significant (P<0.05), but still slightly lower than the control group, but the difference was not statistically significant. CONCLUSION: More in-depth study of viral myocarditis in patients with immune injury mechanism will help to better guide the treatment, and has important clinical significance.