Genomic and Glycolytic Entropy Are Reliable Radiogenomic Heterogeneity Biomarkers for Non-Small Cell Lung Cancer.

Radiogenomic heterogeneity features in 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) have become popular in non-small cell lung cancer (NSCLC) research. However, the reliabilities of genomic heterogeneity features and of PET-based glycolytic features in different image matrix sizes have yet to be thoroughly tested. We conducted a prospective study with 46 NSCLC patients to assess the intra-class correlation coefficient (ICC) of different genomic heterogeneity features. We also tested the ICC of PET-based heterogeneity features from different image matrix sizes. The association of radiogenomic features with clinical data was also examined. The entropy-based genomic heterogeneity feature (ICC = 0.736) is more reliable than the median-based feature (ICC = -0.416). The PET-based glycolytic entropy was insensitive to image matrix size change (ICC = 0.958) and remained reliable in tumors with a metabolic volume of <10 mL (ICC = 0.894). The glycolytic entropy is also significantly associated with advanced cancer stages (p = 0.011). We conclude that the entropy-based radiogenomic features are reliable and may serve as ideal biomarkers for research and further clinical use for NSCLC.

[Associations Among Changes in Meridian Energy, Quality of Life During Surgery, and Prognoses in Newly Diagnosed Lung Cancer Patients: A Longitudinal Study].

BACKGROUND: Approximately 30% of patients experience postoperative complications after surgery for early-stage lung cancer. However, the relationships among meridian energy during lung cancer surgery, changes in quality of life, and prognosis have not been investigated. PURPOSE: This study was designed to explore the associations among meridian energy, changes in quality of life, and prognosis in patients with newly diagnosed lung cancer undergoing surgery. METHODS: A longitudinal, repeated-measures design was used. Basic data forms, meridian energy measurements, and a concise 12-item health status questionnaire were administered to the participants at the time of diagnosis, 2 weeks post-surgery, and 12 weeks post-surgery. During this period, changes were analyzed, and their association with postoperative risks was explored. RESULTS: Forty-eight cases were investigated. Both meridian energy and quality of life were found to be significantly decreased 2 weeks after surgery. The high/low ratio of meridian energy, the physical component score of the Short Form 12-Item Health Survey Questionnaire, gender, cancer stage, and body mass index were identified as significantly associated with prognosis. CONCLUSIONS / IMPLICATIONS FOR PRACTICE: Conclusion/Implications for Practice: The declining trends in meridian energy and quality of life during the 2 weeks after surgery in patients with lung cancer are associated with poor postoperative prognoses. Nurses may use the findings of this study to identify patients at high risk of postoperative complications and develop appropriate strategies to provide comprehensive care.

Inflammatory and Nutritional Biomarkers in Patients With Esophageal Squamous Cell Carcinoma Undergoing Neoadjuvant Chemotherapy and Radiation Therapy.

OBJECTIVES: To investigate the relationship between pretreatment inflammatory and nutritional biomarkers in patients with esophageal squamous cell carcinoma (ESCC) undergoing neoadjuvant chemotherapy and radiation therapy (nCRT). SAMPLE & SETTING: 213 patients with newly diagnosed stage II-III ESCC who received nCRT at an academic hospital in Taiwan. METHODS & VARIABLES: Electronic health record data were used. Records on inflammatory and nutritional biomarkers and clinical outcomes were extracted. Logistic regression analysis was used to predict treatment-related adverse events, Cox regression was used for survival outcomes, and receiver operating characteristic curve analysis was used to determine optimal cutoff values. RESULTS: There was a significant association between low prognostic nutritional index (PNI) and nCRT toxicities and survival. Advanced cancer stage, high platelet-to-lymphocyte ratio, and occurrence of pneumonia/infection were linked to survival outcomes. IMPLICATIONS FOR NURSING: PNI shows promise in predicting prognosis, helps identify high-risk patients, and enables nurses to apply tailored interventions.

The combined tumor-nodal glycolytic entropy improves survival stratification in nonsmall cell lung cancer with locoregional disease.

OBJECTIVE: To investigate whether combining primary tumor and metastatic nodal glycolytic heterogeneity on 18 F-fluorodeoxyglucose PET ( 18 F-FDG PET) improves prognostic prediction in nonsmall cell lung cancer (NSCLC) with locoregional disease. METHODS: We retrospectively analyzed 18 F-FDG PET-derived features from 94 patients who had undergone curative treatments for regional nodal metastatic NSCLC. Overall survival (OS) and progression-free survival (PFS) were analyzed using univariate and multivariate Cox regression models. We used the independent prognosticators to construct models to predict survival. RESULTS: Combined entropy (entropy derived from the combination of the primary tumor and metastatic nodes) and age independently predicted OS (both P = 0.008) and PFS ( P = 0.007 and 0.050, respectively). At the same time, the Eastern Cooperative Oncology Group status was another independent risk factor for unfavorable OS ( P = 0.026). Our combined entropy-based models outperformed the traditional staging system (c-index = 0.725 vs. 0.540, P < 0.001 for OS; c-index = 0.638 vs. 0.511, P = 0.003 for PFS) and still showed prognostic value in subgroups according to sex, histopathology, and different initial curative treatment strategies. CONCLUSION: Combined primary tumor-nodal glycolytic heterogeneity independently predicted survival outcomes. In combination with clinical risk factors, our models provide better survival predictions and may enable tailored treatment strategies for NSCLC with locoregional disease.

Comprehensive Assessment of the Clinical Risk Factors of Postoperative Adverse Events and Survival in Patients With Non-small-cell Lung Cancer.

BACKGROUND/AIM: Postoperative adverse events are associated with poor clinical outcomes and survival in patients with non-small-cell lung cancer (NSCLC) treated with curative operation. However, comprehensive evaluation of the clinical characteristics associated with postoperative adverse events and survival outcomes is lacking. PATIENTS AND METHODS: A retrospective study that evaluated patients with NSCLC who underwent curative surgery between 2008 and 2019 was conducted in a medical center. The baseline characteristics, five-item modified frailty index, sarcopenia, inflammatory biomarkers, surgical approach, postoperative adverse events, and survival were statistically analyzed. RESULTS: Patients with a history of smoking and preoperative sarcopenia were at a higher risk of developing postoperative pulmonary complications. Smoking, frailty, and traditional open thoracotomy (OT) were associated with infections, and sarcopenia was identified as a risk factor for major complications. Advanced tumor stage, high neutrophil-to-lymphocyte ratio, OT, major complications, and infections were identified as risk factors for overall and disease-free survival. CONCLUSION: Pre-treatment sarcopenia was found to be a predictor of major complications. Infections and major complications were associated with survival outcomes in patients with NSCLC.

Glucose metabolic heterogeneity correlates with pathological features and improves survival stratification of resectable lung adenocarcinoma.

OBJECTIVE: We investigated whether glycolytic heterogeneity correlated with histopathology, and further stratified the survival outcomes pertaining to resectable lung adenocarcinoma. METHODS: We retrospectively analyzed the 18F-fluorodeoxyglucose positron emission tomography-derived entropy and histopathology from 128 patients who had undergone curative surgery for lung adenocarcinoma. Disease-free survival (DFS) and overall survival (OS) were analyzed using univariate and multivariate Cox regression models. Independent predictors were used to construct survival prediction models. RESULTS: Entropy significantly correlated with histopathology, including tumor grades, lympho-vascular invasion, and visceral pleural invasion. Furthermore, entropy was an independent predictor of unfavorable DFS (p = 0.031) and OS (p = 0.004), while pathological nodal metastasis independently predicted DFS (p = 0.009). Our entropy-based models outperformed the traditional staging system (c-index = 0.694 versus 0.636, p = 0.010 for DFS; c-index = 0.704 versus 0.630, p = 0.233 for OS). The models provided further survival stratification in subgroups comprising different tumor grades (DFS: HR = 2.065, 1.315, and 1.408 for grade 1-3, p = 0.004, 0.001, and 0.039, respectively; OS: HR = 25.557, 6.484, and 2.570, for grade 1-3, p = 0.006, < 0.001, and = 0.224, respectively). CONCLUSION: The glycolytic heterogeneity portrayed by entropy is associated with aggressive histopathological characteristics. The proposed entropy-based models may provide more sophisticated survival stratification in addition to histopathology and may enable personalized treatment strategies for resectable lung cancer.

A comparison of 18 F-FDG PET-based radiomics and deep learning in predicting regional lymph node metastasis in patients with resectable lung adenocarcinoma: a cross-scanner and temporal validation study.

OBJECTIVE: The performance of 18 F-FDG PET-based radiomics and deep learning in detecting pathological regional nodal metastasis (pN+) in resectable lung adenocarcinoma varies, and their use across different generations of PET machines has not been thoroughly investigated. We compared handcrafted radiomics and deep learning using different PET scanners to predict pN+ in resectable lung adenocarcinoma. METHODS: We retrospectively analyzed pretreatment 18 F-FDG PET from 148 lung adenocarcinoma patients who underwent curative surgery. Patients were separated into analog (n = 131) and digital (n = 17) PET cohorts. Handcrafted radiomics and a ResNet-50 deep-learning model of the primary tumor were used to predict pN+ status. Models were trained in the analog PET cohort, and the digital PET cohort was used for cross-scanner validation. RESULTS: In the analog PET cohort, entropy, a handcrafted radiomics, independently predicted pN+. However, the areas under the receiver-operating-characteristic curves (AUCs) and accuracy for entropy were only 0.676 and 62.6%, respectively. The ResNet-50 model demonstrated a better AUC and accuracy of 0.929 and 94.7%, respectively. In the digital PET validation cohort, the ResNet-50 model also demonstrated better AUC (0.871 versus 0.697) and accuracy (88.2% versus 64.7%) than entropy. The ResNet-50 model achieved comparable specificity to visual interpretation but with superior sensitivity (83.3% versus 66.7%) in the digital PET cohort. CONCLUSION: Applying deep learning across different generations of PET scanners may be feasible and better predict pN+ than handcrafted radiomics. Deep learning may complement visual interpretation and facilitate tailored therapeutic strategies for resectable lung adenocarcinoma.

Risk factor analysis of postoperative complications after adjunctive pulmonary resection in patients with multidrug-resistant tuberculosis: A multi-institutional study.

BACKGROUND AND OBJECTIVE: Multidrug-resistant tuberculosis (MDR-TB) requires extended treatment with regimens with multiple side effects, resulting in high treatment failure rates. Adjunctive lung resection combined with anti-tubercular agents improves outcomes. However, few studies have evaluated the potential harm from surgery and determined the optimal conditions for surgery. We aimed to analyze perioperative conditions to assess risk factors for postoperative complications in a multi-institutional setting. METHODS: This retrospective study included 44 patients with MDR-TB who underwent adjunctive lung resection at three management groups of the Taiwan MDR-TB consortium between January 2007 and December 2020. Demographic data, clinical characteristics, radiological findings, sputum culture status before surgery, primary or acquired drug resistance, surgical procedure, complications, and treatment outcomes were collected and analyzed. Multivariate logistic regression was used to identify risk factors for postoperative complications. RESULTS: Twenty-seven patients (61.4%) underwent lung resection using video-assisted thoracic surgery (VATS). The overall surgical complication rate was 20.5%, and the surgical mortality rate was 9.1%. Postsurgical hemothorax was the most common complication (11.4%). According to the univariate analysis, hilum involvement in images, positive preoperative sputum culture, and thoracotomy approach were unfavorable factors. VATS approach [adjusted OR, 0.088 (95% CI, 0.008-0.999)] was the only favorable factor identified by multivariate analysis. CONCLUSION: The minimally invasive approach is a growing trend, and lobectomies and sublobar resections were the main procedures for MDR-TB. The VATS approach significantly reduced the surgical complication rate. Postsurgical hemothorax was noteworthy, and meticulous hemostasis of the chest wall and residual lung surface is critical for successful resections.

Prognostic Values of Inflammatory Indexes and Clinical Factors in Patients with Epidermal Growth Factor Receptor Mutations in Lung Adenocarcinoma and Treated with Tyrosine Kinase Inhibitors.

This study aimed to access the predictive value of inflammatory indices and clinical factors in toxicity and survival in patients with epidermal growth factor receptor (EGFR)-mutated lung adenocarcinoma receiving first-line tyrosine kinase inhibitor (TKI)-treatment. A total of 259 patients with stage IIIB−IV lung adenocarcinoma and actionable EGFR mutation who received first-line TKI treatment between 2008 and 2020 were retrospectively enrolled and analyzed. The prognostic factors of TKI-related toxicity, overall survival (OS), and progression-free survival (PFS) were identified by using logistic regression analysis and Cox proportional hazards models. Pre-TKI high platelet-to-lymphocyte ratio (PLR) was associated with post-TKI anemia. Hypoalbuminemia was associated with acneiform rash. Elderly age (≥70 years) and lower body mass index (<18.5 kg/m2) were also associated with hypoalbuminemia. Elderly age, stage IV, EGFR-mutated with L858R and uncommon mutations, and neutrophil-to-lymphocyte ratio were found to be independent prognostic factors for PFS, while elderly age, uncommon EGFR-related mutations, and lymphocyte-to-monocyte ratio were found to be independent prognostic factors for OS. A useful prognostic scoring tool for improving the survival risk stratification of patients was established by incorporating the above essential factors. Baseline hypoalbuminemia and PLR could be crucial clinical assessment factors when initiating TKI therapy. In addition, the optimization of individualized treatment strategies for these patients may be assisted by using the risk-scoring model.

Tumor glycolytic heterogeneity improves detection of regional nodal metastasis in patients with lung adenocarcinoma.

OBJECTIVE: The diagnostic performance of 18F-FDG PET for detecting regional lymph node metastasis in resectable lung cancer is variable, and its sensitivity for adenocarcinoma is even lower. We aimed to evaluate the value of 18F-FDG PET-derived features in predicting pathological lymph node metastasis in patients with lung adenocarcinoma. METHODS: We retrospectively analyzed pretreatment 18F-FDG PET-derived features of 126 lung adenocarcinoma patients who underwent curative surgery. A logistic regression model was used to analyze the association between study variables and pathological regional lymph node status obtained from the curative surgery. Furthermore, Cox regression analysis was used to test the effect of the study variables on survival outcomes, including disease-free survival (DFS) and overall survival (OS). RESULTS: The primary tumor entropy (OR = 1.7, p = 0.014) and visual interpretation of regional nodes via 18F-FDG PET (OR = 2.5, p = 0.026) independently predicted pathological regional lymph node metastasis. The areas under the receiver-operating-characteristic curves were 0.631, 0.671, and 0.711 for visual interpretation, primary tumor entropy, and their combination, respectively. Based on visual interpretation, a primary tumor entropy ≥ 3.0 improved the positive predictive value of positive visual interpretation from 51.2% to 63.0%, whereas an entropy < 3.0 improved the negative predictive value of negative visual interpretation from 75.3% to 82.6%. In cases with positive visual interpretation and low entropy, or negative visual interpretation and high entropy, the nodal metastasis rates were approximately 30%. In the survival analyses, the primary tumor entropy was also independently associated with DFS (HR = 2.7, p = 0.001) and OS (HR = 4.8, p = 0.001). CONCLUSIONS: Our preliminary results show that the primary tumor entropy may improve 18F-FDG PET visual interpretation in predicting pathological nodal metastasis in lung adenocarcinoma, and may also show a survival prognostic value. This versatile biomarker may facilitate tailored therapeutic strategies for patients with resectable lung adenocarcinoma.

Quality improvements of antimicrobial prophylaxis in coronary artery bypass grafting.

BACKGROUND: Although the principles of antibiotics prophylaxis are well established, more than 60% of hospitals that joined the international quality indicator project failed to discontinue the use of prophylactic antibiotics within 24h after coronary artery bypass grafting (CABG). Our specific aims are to disseminate the gain obtained from breakthrough series model in knee arthroplasty and abdominal hysterectomy to increase the rate of prophylactic duration not longer than 24h in patients with CABG. METHODS: The control and intervention groups enrolled 55 and 78 patients with CABG before and after the project. Measurements were prophylactic interval and duration, surgical site infection, hospital and antibiotics costs. Two strategies were developed. The key cardiac surgeon was invited to attend quality improvement activities. Knowledge and rationale of medical quality indicators would thus be communicated. Secondly, we proposed a regional symposium in which a level of competition was subconsciously established, and practitioners would present their level of compliance. RESULTS: Instances of prophylactic interval within 1h prior to incision were significantly increased from 66.7% to 97.4%. Rates of prophylactic duration less than 24h were significantly increased from 2.8% to 66.1%. The average hospital cost was reduced by 16.4%, and antibiotics cost was reduced by 91.8%. No significant changes in surgical site infection within 30 d of CABG were observed. CONCLUSIONS: We successfully disseminated the gain of breakthrough project in improving antimicrobial prophylaxis to CABG. By implementing this model, we are able to optimize the timing and duration of antimicrobial prophylaxis in patients with CABG to a level above worldwide average.

Perioperative exercise intervention in patients with lung cancer: A systematic literature review of randomized controlled trials.

OBJECTIVES: During perioperative, lung cancer (LC) patients are often left to experience debilitating disease-related symptoms, impaired physical activity and health-related quality of life (HRQoL), and social difficulties, despite the progress achieved in terms of treatment efficacy. Nonpharmacological intervention, such as exercise, has been identified as an effective strategy in LC patients before and after lung resection. Therefore, we aimed to assess evidence of the effect of perioperative exercise among patients with LC. MATERIALS AND METHODS: Seven databases were searched from January 1998 to September 2020. All randomized controlled trials (RCTs) that evaluated the effect of exercise on the physical and psychological status of patients with LC during the perioperative period were reviewed. Two reviewers independently assessed the quality of all studies included here using the revised Cochrane risk of bias tool for RCTs. RESULTS: Seventeen RCTs (1199 participants) published between 2011 and 2019 met for this literature review. The outcome measures that emerged from these studies included subjective outcomes, such as HRQoL, pain score, fatigue, and objective effects, such as cardiorespiratory fitness, pulmonary function, physical activity, and biological markers. Overall, these studies suggest that exercise should be an optimal option for LC; however, its efficacy and effectiveness regarding HRQoL should be investigated further. CONCLUSION: Perioperative exercise could be included in the rehabilitation program of patients with LC. More extensive, high-quality RCTs evidence is needed on the ideal exercise type, duration, intensity, and timing across the LC perioperative care.

Prognostic Value of Combing Primary Tumor and Nodal Glycolytic-Volumetric Parameters of 18F-FDG PET in Patients with Non-Small Cell Lung Cancer and Regional Lymph Node Metastasis.

We investigated whether the combination of primary tumor and nodal 18F-FDG PET parameters predict survival outcomes in patients with nodal metastatic non-small cell lung cancer (NSCLC) without distant metastasis. We retrospectively extracted pre-treatment 18F-FDG PET parameters from 89 nodal-positive NSCLC patients (stage IIB-IIIC). The Cox proportional hazard model was used to identify independent prognosticators of overall survival (OS) and progression-free survival (PFS). We devised survival stratification models based on the independent prognosticators and compared the model to the American Joint Committee on Cancer (AJCC) staging system using Harrell's concordance index (c-index). Our results demonstrated that total TLG (the combination of primary tumor and nodal total lesion glycolysis) and age were independent risk factors for unfavorable OS (p < 0.001 and p = 0.001) and PFS (both p < 0.001), while the Eastern Cooperative Oncology Group scale independently predicted poor OS (p = 0.022). Our models based on the independent prognosticators outperformed the AJCC staging system (c-index = 0.732 versus 0.544 for OS and c-index = 0.672 versus 0.521 for PFS, both p < 0.001). Our results indicate that incorporating total TLG with clinical factors may refine risk stratification in nodal metastatic NSCLC patients and may facilitate tailored therapeutic strategies in this patient group.

Prognostic value of peak lactate during cardiopulmonary bypass in adult cardiac surgeries: A retrospective cohort study.

OBJECTIVE: Tissue hypoperfusion during cardiopulmonary bypass (CPB) affects cardiac surgical outcomes. Lactate, an end product of anaerobic glycolysis from oxygen deficit, is a marker of tissue hypoxia. In this study, we aimed to identify the prognostic value of blood lactate level during CPB in predicting outcomes in adults undergoing cardiac surgeries. MATERIALS AND METHODS: We retrospectively reviewed the medical records of patients who underwent cardiac surgeries with CPB from January 2015 to December 2015. Data about the characteristics of patients, preoperative status, type of surgery, and intraoperative lactate levels were collected. The outcomes were in-hospital mortality and complications. The receiver operating characteristics (ROC) curves were used to assess the ability of peak lactate level during CPB in predicting in-hospital mortality. RESULTS: A total of 97 patients, including 61 who underwent emergent or urgent surgery, were enrolled. The types of surgery included coronary artery bypass grafting (CABG, n = 52), valve surgery (n = 27), combined surgery (CABG and valve surgery, n = 4), great vessel surgery (including aortic dissection, n = 9), and others (n = 5). The median CPB time was 139 min (interquartile range = 120-175). The median initial lactate and peak lactate levels during CPB were 0.9 and 4.2 mmol/L, respectively. In-hospital mortality was 14.4%, which was significantly associated with age and peak lactate level in the multivariate logistic regression model. When the peak lactate level during CPB reached 7.25 mmol/L, in-hospital mortality could be predicted with an area under the ROC curve of 0.75 (95% confidence interval: 0.59-0.90; P = 0.003), with a sensitivity of 57% and specificity of 93%. CONCLUSION: Hyperlactatemia during CPB was associated with increased in-hospital mortality. Thus, early detection of such conditions and aggressive postoperative care are important.

Metastatic Parathyroid Hormone-Secreting Prostate Adenocarcinoma Mimicking Ectopic Parathyroid Adenoma Demonstrated on 99mTc-MIBI Image.

Tc-MIBI has long been used to localize hyperfunctioning parathyroid tissue in patients with hyperparathyroidism. This tracer can also concentrate in various neoplastic tissues including prostate adenocarcinoma. We herein report a case with parathyroid hormone-secreting metastatic prostate cancer mimicking an ectopic parathyroid adenoma on the Tc-MIBI scan. We conclude that metastatic prostate cancer should be included as one of the differential diagnoses when interpreting Tc-MIBI scan.

Resection of a cavernous hemangioma of the posterior mediastinum by sclerotherapy and uniport thoracoscopic surgery.

A 44-year-old female presented with cavernous hemangioma of the posterior mediastinum. Imaging revealed that it was approximately 2 cm in size and without an arterial supply from either the thoracic aorta or intercostal artery. The patient was treated with intraoperative sclerotherapy and hemangioma resection by uniport thoracoscopic surgery via a small 3-cm surgical wound. The surgical outcome and follow-up were good.

Hematologic Markers as Prognostic Factors in Nonmetastatic Esophageal Cancer Patients under Concurrent Chemoradiotherapy.

Nonmetastatic esophageal cancer can demonstrate a high local recurrence rate even under the standard treatment. We evaluated platelet counts before and after concurrent chemoradiotherapy (CCRT), neutrophil-to-lymphocyte ratio, and platelet-to-lymphocyte ratio for predicting esophageal cancer prognosis under CCRT. Newly diagnosed patients with esophageal cancer (stages IA-IIIC) who underwent CCRT during January 2013-December 2017 were enrolled. The data were collected retrospectively. Overall survival (OS), time to progressive disease (TPD), and time to metastasis (TM) were recorded for indicating prognosis. Kaplan-Meier curves were plotted and univariate and multivariate analyses were performed. In total, 105 patients were enrolled. The stages of esophageal cancer and surgery were associated with prognosis (i.e., OS, TPD, and TM). Based on TPD and TM, women had better prognosis than men. In the univariate analysis, high pre- and post-CCRT platelet counts (>300,000/µL), platelet-to-lymphocyte ratio (PLR), and neutrophil-to-lymphocyte ratio (NLR) as well as low lymphocyte percentage were significantly associated with poor prognosis. However, in the multivariate analysis, only post-CCRT high platelet count (>300,000/µL) remained significantly associated with poor prognosis (P = .041, .045, and .023 for OS, TPD, and TM, respectively). Poor prognosis was observed in patients with high platelet counts, PLR, NLR, and low lymphocyte percentage. Surgery was an independent factor predicting better prognosis. Our findings may have clinical significance with regard to therapeutic decision-making.

Enteral Access Potentially Endangers Esophageal Carcinoma Patients Under Multi-modality Therapy: A Population-based Study.

BACKGROUND/AIM: This study aimed to evaluate the clinical outcome of esophageal cancer (EC) patients with enteral access (EA) undergoing multimodality therapy. PATIENTS AND METHODS: This retrospective study analyzed data between 1997 and 2012 in Taiwan using the National Health Insurance Research Database. Patients with newly-diagnosed EC undergoing multimodality therapy were identified and classified as either EA group or no-EA group. RESULTS: The mortality incidence of EC patients with EA was significantly higher than in no-EA patients. The Cox model revealed the EA group had a higher risk of mortality than the no-EA group. Patients with chronic obstructive pulmonary disease (COPD) were at significantly higher risk of mortality compared to patients without COPD. CONCLUSION: EA in EC patients undergoing multimodality therapy was associated with an increased risk of mortality.

Combining the radiomic features and traditional parameters of 18F-FDG PET with clinical profiles to improve prognostic stratification in patients with esophageal squamous cell carcinoma treated with neoadjuvant chemoradiotherapy and surgery.

OBJECTIVES: To investigate the role of the traditional and radiomic parameters of 18F-FDG PET for predicting the outcomes of patients with esophageal squamous cell carcinoma (SqCC). METHODS: Forty-four patients with primary esophageal SqCC who underwent neoadjuvant chemoradiotherapy (CCRT) followed by esophagectomy (tri-modality treatment) were retrospectively analyzed. All patients underwent 18F-FDG PET/CT before and after neoadjuvant CCRT. The radiomic features were calculated using the pre-treatment PET scan. Pre-treatment radiomic features and changes in the PET-derived traditional parameters after neoadjuvant CCRT were analyzed according to the pathological response to esophagectomy, disease-free survival (DFS), and overall survival (OS). We further developed a scoring system based on the independent survival prognosticators and compared our model to the traditional TNM staging system and surgical pathology. RESULTS: A pre-treatment primary tumor histogram entropy ≥ 3.69 predicts an unfavorable response to neoadjuvant CCRT (OR = 19.25, p = 0.009). An SUVmax reduction ratio ≤ 0.76, a pre-treatment primary tumor code similarity ≤ 0.0235, and incomplete pathological remission were independently associated with poor OS (p = 0.019, 0.033, and 0.038, respectively) and DFS (p = 0.049, 0.021, and 0.009, respectively). The three survival prognosticators were used to construct a scoring system (score 0-1, 2, and 3). Patients with a score of 2 or 3 had a significantly worse survival outcome than those with a score of 0-1 (HRs for OS: 3.58 for score 2, and 15.19 for score 3, p < 0.001; HRs for DFS: 1.39 for score 2 and 6.04 for score 3, p = 0.001).This survival prediction model was superior to the traditional TNM staging system (p < 0.001 versus p = 0.061 for OS, and p = 0.001 versus p = 0.027 for DFS) and the model based on surgical pathology (p < 0.001 versus p = 0.049 for OS, and p = 0.001 versus p = 0.022 for DFS). CONCLUSIONS: The 18F-FDG PET-derived radiomic parameter is useful for predicting the surgical pathological response in patients with esophageal SqCC treated with the tri-modality method. Using a combination of traditional and radiomic PET parameters with clinical profiles enables better stratification of patients into subgroups with various survival rates.

Natriuretic peptides cause relaxation of human esophageal mucosal muscle.

Natriuretic peptides have been demonstrated to cause relaxation of the human gallbladder muscle through interaction with natriuretic peptide receptor-B (NPR-B/NPR2). Effects of natriuretic peptides in the human esophageal muscle were unknown. To investigate the effects of natriuretic peptides in the human esophagus, we measured relaxation of muscularis mucosae strips isolated from the human esophagus caused by C-type natriuretic peptide (CNP), brain natriuretic peptide (BNP), atrial natriuretic peptide (ANP) and des[Gln(18), Ser(19), Gly(20), Leu(21), Gly(22)]ANP(4-23) amide (cANP(4-23)), a selective natriuretic peptide receptor-C (NPR-C) agonist. In endothelin-1 or carbachol-contracted mucosal muscle strips, CNP caused moderate, sustained and concentration-dependent relaxation. BNP caused a very mild relaxation whereas ANP and cANP(4-23) did not cause any relaxation. CNP was much more potent than BNP and ANP in causing relaxation. These suggest the existence of NPR-B mediating relaxation. The CNP-induced relaxation was not affected by tetrodotoxin or atropine in endothelin-1-contracted esophageal strips and not by tetrodotoxin in carbachol-contracted strips, indicating a direct effect of CNP on the human esophageal muscularis mucosae. Taken together, these results demonstrate that natriuretic peptides cause relaxation of the muscularis mucosae of the human esophagus and suggest that the relaxation is through interaction with NPR-B. Natriuretic peptides may play an important role in the control of human esophageal motility.