Monodisperse Plant Protein Nanoparticles Prepared by Cation-Exchange Resins for Stabilization of Pickering Emulsions.

Our understanding of the microstructure of many plant proteins is based on the ancient and conventional methods of alkali extraction and acid precipitation, which generate considerable amounts of NaCl causing salting-out effects and aggregation of their molecules. In this study, monodisperse rice protein (RP) nanoparticles were prepared using cation-exchange resins that release H+ and absorb Na+, thus avoiding the generation of NaCl during neutralization of the alkali extracts. The generated RP nanoparticles of small diameter (20 nm) and excellent uniformity (0.17 polydispersity) quickly diffuse to and stabilize the oil-water interface, producing oil-in-water Pickering emulsions. The emulsifying ability and emulsion stability afforded with these nanoparticles were 17 and 3.5 times higher than those of nanoparticles prepared by conventional alkali extraction and acid precipitation methods, respectively. Furthermore, increased RP nanoparticle concentration created more stable emulsions with smaller droplets and reduced flocculation index vital for practical applications. This study provides a convincing example of how to prepare monodisperse protein nanoparticles that adsorb at a fluid interface, which may find numerous applications in food and cosmetic formulations.

Intercepting Medication Errors in Pediatric In-patients Using a Prescription Pre-audit Intelligent Decision System: A Single-center Study.

OBJECTIVES: Medication errors can happen at any phase of the medication process at health care settings. The objective of this study is to identify the characteristics of severe prescribing errors at a pediatric hospital in the inpatient setting and to provide recommendations to improve medication safety and rational drug use. METHODS: This descriptive retrospective study was conducted at a tertiary pediatric hospital using data collected from Jan. 1st, 2019 to Dec. 31st, 2020. During this period, the Prescription Pre-audit Intelligent Decision System was implemented. Medication orders with potential severe errors would trigger a Level 7 alert and would be intercepted before it reached the pharmacy. Trained pharmacists maintained the system and facilitated decision making when necessary. For each order intercepted by the system the following patient details were recorded and analyzed: patient age, patient's department, drug classification, dosage forms, route of administration, and the type of error. RESULTS: A total of 2176 Level 7 medication orders were intercepted. The most common errors were associated with drug dosage, administration route, and dose frequency, accounting for 35.2%, 32.8% and 13.2%, respectively. Of all the intercepted oerrors. 53.6% occurred in infants aged < 1 year. Administration routes involved were mainly intravenous, oral and external use drugs. Most alerts came from the neonatology department and constituted 40.5% of the total alerts, followed by the nephrology department 15.9% and pediatric intensive care unit (PICU) 11.3%. As to dosage forms, injections accounted for 50.4% of alerts, with 21.3% attributable to topical solutions, 9.1% to tablets, and 5.7% to inhalation. Anti-infective agents were the most common therapeutic drugs prescribed with errors. CONCLUSIONS: The Prescription Pre-audit Intelligent Decision System, with the supervision of trained pharmacists can validate prescriptions, increase prescription accuracy, and improve drug safety for hospitalized children. It is a medical service model worthy of consideration.

First-line or second-line PD-1 inhibition in advanced oesophageal squamous cell carcinoma: A prospective, multicentre, registry study.

WHAT IS KNOWN AND OBJECTIVE: First-line and second-line immunotherapy with programmed death-1 (PD-1) inhibitors both improve overall survival in patients with advanced oesophageal squamous cell cancer (ESCC). This study explored survival differences between first-line and second-line PD-1 inhibition in advanced ESCC. METHODS: This registry study included 167 patients with advanced ESCC who were exposed to PD-1 inhibitors in either a first-line or a second-line setting between 15 January 2019 and 31 October 2020. The primary endpoint was overall survival, and secondary endpoints included overall tumour response, progression-free survival (PFS) and PFS2. A propensity score-matching (PSM) analysis was performed using the nearest-neighbour method. RESULTS AND DISCUSSION: Sixty-one patients started first-line treatment with chemotherapy and a PD-1 inhibitor (Group 1), while 106 started chemotherapy as the first-line choice and received a PD-1 inhibitor as the second-line choice (Group 2). The median PFS was 7.1 months in Group 1 and 4.1 months in Group 2 (log-rank p = 0.001). The median PFS2 was 7.1 months in Group 1 and 7.4 months in Group 2 (log-rank p = 0.4). Before PSM, the median overall survival was 13.5 months in Group 1 and 14.1 months in Group 2 (log-rank p = 0.9), and the sensitivity analysis showed consistent results (14.0 vs. 14.1 months). After PSM, the median overall survival rates for Group 1 (n = 61) and Group 2 (n = 61) were 13.5 and 13.1 months (log-rank p = 0.7) respectively. WHAT IS NEW AND CONCLUSION: In this study, patients with advanced ESCC who received first-line or second-line PD-1 inhibitors seemed to have comparable overall survival.

Thoracic para-aortic lymph node recurrence in patients with esophageal squamous cell carcinoma: A propensity score-matching analysis.

BACKGROUND: Thoracic para-aortic lymph node (TPLN) recurrence in esophageal squamous cell carcinoma (ESCC) is rare and its impact on survival is unknown. We studied survival in patients with ESCC who developed TPLN recurrence. AIM: To study the survival in patients with ESCC who developed TPLNs recurrence. METHODS: Data were collected retrospectively for 219 patients who had undergone curative surgery for ESCC during January 2012 to November 2017 and who developed recurrences (36.29% of 604 patients who had undergone curative surgeries for ESCC). The patients were classified into positive (+) and negative (-) TPLN metastasis subgroups. We also investigated TPLN recurrence in 223 patients with ESCC following definitive chemoradiotherapy during 2012-2013. Following propensity score matching (PSM) and survival estimation, factors predictive of overall survival (OS) were explored using a Cox proportional hazards model. RESULTS: Among the patients with confirmed recurrence, 18 were TPLN (+) and 13 developed synchronous distant metastases. Before PSM, TPLN (+) was associated with worse recurrence-free (P = 0.00049) and OS [vs TPLN (-); P = 0.0027], whereas only the intergroup difference in recurrence-free survival remained significant after PSM (P = 0.013). The Cox analysis yielded similar results. Among the patients who had received definitive chemoradiotherapy, 3 (1.35%) had preoperative TPLN enlargement and none had developed recurrences. CONCLUSION: TPLN metastasis is rare but may be associated with poor survival.

Neoadjuvant Chemotherapy in Early Triple-Negative Breast Cancer: A Pairwise and Network Meta-Analysis of Pathological Complete Response.

We performed a pairwise and network meta-analysis to compare pathological complete response (pCR) among neoadjuvant chemotherapy in patients with triple-negative breast cancer. We searched PubMed for randomized clinical trials between January 1, 2000 and December 1, 2020. Abstracts from meetings were also searched. A frequentist random-effect model was applied to compare pCR and toxicities. The P-score was used to rank treatment effects. Nineteen trials with 16 treatments and 7794 patients were included. On the basis of SoC, the addition of carboplatin (OR = 1.82, 95% CI, 1.24 to 2.68, P < .01) and the addition of checkpoint inhibitors (OR = 1.69, 95% CI, 1.23 to 2.32, P < .01) increased pCR in pairwise meta-analysis; compared with paclitaxel, nab-paclitaxel did not improve pCR rates (OR = 1.81, 95% CI, .80 to 4.12, P = .16). The anthracycline-sparing regimen led to similar pCR compared with the anthracycline-containing regimen (OR = 1.50, 95% CI, .82 to 2.76, P = .19). In network meta-analysis, the addition of carboplatin plus a PD-1 inhibitor (pembrolizumab), carboplatin plus bevacizumab, and carboplatin plus veliparib ranked as the top three treatments for achieving pCR, with corresponding P-scores of .91, .84, and .72, respectively. Among patients with homologous recombination deficiency, the addition of carboplatin (OR = 1.31, 95% CI, .69 to 2.50, P = .41) or carboplatin plus PARP inhibitors (OR = 1.19, 95% CI, .58 to 2.47, P = .63) did not increase pCR. For triple-negative breast cancer, combining carboplatin with taxane-anthracycline-containing neoadjuvant chemotherapy could be the standard of care, and the combination containing checkpoint inhibitor is promising. However, their role in long-term oncologic outcome remains to be determined.

Development and validation of a radiomics-based model to predict local progression-free survival after chemo-radiotherapy in patients with esophageal squamous cell cancer.

PURPOSE: To develop a nomogram model for predicting local progress-free survival (LPFS) in esophageal squamous cell carcinoma (ESCC) patients treated with concurrent chemo-radiotherapy (CCRT). METHODS: We collected the clinical data of ESCC patients treated with CCRT in our hospital. Eligible patients were randomly divided into training cohort and validation cohort. The least absolute shrinkage and selection operator (LASSO) with COX regression was performed to select optimal radiomic features to calculate Rad-score for predicting LPFS in the training cohort. The univariate and multivariate analyses were performed to identify the predictive clinical factors for developing a nomogram model. The C-index was used to assess the performance of the predictive model and calibration curve was used to evaluate the accuracy. RESULTS: A total of 221 ESCC patients were included in our study, with 155 patients in training cohort and 66 patients in validation cohort. Seventeen radiomic features were selected by LASSO COX regression analysis to calculate Rad-score for predicting LPFS. The patients with a Rad-score ≥ 0.1411 had high risk of local recurrence, and those with a Rad-score < 0.1411 had low risk of local recurrence. Multivariate analysis showed that N stage, CR status and Rad-score were independent predictive factors for LPFS. A nomogram model was built based on the result of multivariate analysis. The C-index of the nomogram was 0.745 (95% CI 0.7700-0.790) in training cohort and 0.723(95% CI 0.654-0.791) in validation cohort. The 3-year LPFS rate predicted by the nomogram model was highly consistent with the actual 3-year LPFS rate both in the training cohort and the validation cohort. CONCLUSION: We developed and validated a prediction model based on radiomic features and clinical factors, which can be used to predict LPFS of patients after CCRT. This model is conducive to identifying the patients with ESCC benefited more from CCRT.

Factors associated with the time to return negative RT-PCR from COVID-19 in paediatric patients: a retrospective cohort study.

OBJECTIVE: This study aimed to describe the epidemiological and clinical features and potential factors related to the time to return negative reverse transcriptase (RT)-PCR in discharged paediatric patients with COVID-19. DESIGN: Retrospective cohort study. SETTING: Unscheduled admissions to 12 tertiary hospitals in China. PARTICIPANTS: Two hundred and thirty-three clinical charts of paediatric patients with confirmed diagnosis of COVID-19 admitted from 1 January 2020 to 17 April 2020. PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcome measures: factors associated with the time to return negative RT-PCR from COVID-19 in paediatric patients. SECONDARY OUTCOME MEASURES: epidemiological and clinical features and laboratory results in paediatric patients. RESULTS: The median age of patients in our cohort was 7.50 (IQR: 2.92-12.17) years, and 133 (57.1%) patients were male. 42 (18.0%) patients were evaluated as asymptomatic, while 162 (69.5%) and 25 (10.7%) patients were classified as mild or moderate, respectively. In Cox regression analysis, longer time to negative RT-PCR was associated with the presence of confirmed infection in family members (HR (95% CI): 0.56 (0.41 to 0.79)). Paediatric patients with emesis symptom had a longer time to return negative (HR (95% CI): 0.33 (0.14 to 0.78)). During hospitalisation, the use of traditional Chinese medicine (TCM) and antiviral drugs at the same time is less conducive to return negative than antiviral drugs alone (HR (95% CI): 0.85 (0.64 to 1.13)). CONCLUSIONS: The mode of transmission might be a critical factor determining the disease severity of COVID-19. Patients with emesis symptom, complications or confirmed infection in family members may have longer healing time than others. However, there were no significant favourable effects from TCM when the patients have received antiviral treatment.

Effect of sidedness on survival among patients with early-stage colon cancer: a SEER-based propensity score matching analysis.

BACKGROUND: Most previous studies compared survival between left-sided and right-sided colon cancer without adjustment for clinicopathological parameters. We investigated the effect of sidedness on survival among patients with early-stage colon cancer, using a propensity score matching method. METHODS: The 18 registry custom data within the SEER database were used to identify patients who were diagnosed with colon cancer between 2010 and 2014. A propensity score matching analysis was performed using the nearest neighbor method. Survival was estimated using the Kaplan-Meier method. A Cox proportional hazards model was applied to determine the prognostic factors. RESULTS: In the unmatched cohort, 25,094 (35.72%) patients were diagnosed with left-sided colon cancer and 45,156 (64.28%) with right-sided colon cancer. After propensity score matching, each cohort included 5118 patients, and the clinicopathological characteristics were well balanced. In the unmatched cohort, left-sided colon cancer had superior all-cause (χ2=315, P<0.01) and cancer-specific (χ2=43, P<0.01) survival than right-sided tumors. However, in the matched cohort, no difference was observed for all-cause (χ2=0.7, P=0.4) and cancer-specific (χ2=0, P=0.96) survival between left and right colon cancer. The Cox model did not indicate sidedness as a prognostic factor. In the subgroup analysis, stage II right-sided colon cancer had a better survival outcome, while stage III left-sided tumors had a better survival outcome. CONCLUSIONS: After adjusting for clinicopathological characteristics in this study, sidedness showed no impact on survival in early-stage colon cancer. However, sidedness was associated with prognostic differences in stages II and III early-stage colon cancer.

A nomogram based on pretreatment CT radiomics features for predicting complete response to chemoradiotherapy in patients with esophageal squamous cell cancer.

PURPOSE: To develop and validate a nomogram model to predict complete response (CR) after concurrent chemoradiotherapy (CCRT) in esophageal squamous cell carcinoma (ESCC) patients using pretreatment CT radiomic features. METHODS: Data of patients diagnosed as ESCC and treated with CCRT in Shantou Central Hospital during the period from January 2013 to December 2015 were retrospectively collected. Eligible patients were included in this study and randomize divided into a training set and a validation set after successive screening. The least absolute shrinkage and selection operator (LASSO) with logistic regression to select radiomics features calculating Rad-score in the training set. The logistic regression analysis was performed to identify the predictive clinical factors for developing a nomogram model. The area under the receiver operating characteristic curves (AUC) was used to assess the performance of the predictive nomogram model and decision curve was used to analyze the impact of the nomogram model on clinical treatment decisions. RESULTS: A total of 226 patients were included and randomly divided into two groups, 160 patients in training set and 66 patients in validation set. After LASSO analysis, seven radiomics features were screened out to develop a radiomics signature Rad-score. The AUC of Rad-score was 0.812 (95% CI 0.742-0.869, p < 0.001) in the training set and 0.744 (95% CI 0.632-0.851, p = 0.003) in the validation set. Multivariate analysis showed that Rad-score and clinical staging were independent predictors of CR status, with p values of 0.035 and 0.023, respectively. A nomogram model incorporating Rad-socre and clinical staging was developed and validated, with an AUC of 0.844 (95% CI 0.779-0.897) in the training set and 0.807 (95% CI 0.691-0.894) in the validation set. Delong test showed that the nomogram model was significantly superior to the clinical staging, with p < 0.001 in the training set and p = 0.026 in the validation set. The decision curve showed that the nomogram model was superior to the clinical staging when the risk threshold was greater than 25%. CONCLUSION: We developed and validated a nomogram model for predicting CR status of ESCC patients after CCRT. The nomogram model was combined radiomics signature Rad-score and clinical staging. This model provided us with an economical and simple method for evaluating the response of chemoradiotherapy for patients with ESCC.

Prognostic Significance of Baseline Neutrophil Count and Lactate Dehydrogenase Level in Patients With Esophageal Squamous Cell Cancer Treated With Radiotherapy.

Background: This present study aimed to explore the prognostic value of pretreatment neutrophil and lactate dehydrogenase (LDH) and to develop a prognostic risk scoring model to predict prognosis in esophageal squamous cell cancer (ESCC) patients treated with definitive radiotherapy. Methods: Retrospectively collected data of patients who received definitive radiotherapy for ESCC at Shantou Central Hospital between January 2009 and December 2015 were included for the analysis. The association between the level of LDH and neutrophil and clinicopathological characteristics were analyzed. We performed univariate and multivariate analyses to identify the prognostic predictors for patients with ESCC. Based on the results, we also developed a prognostic risk scoring model and assessed its predictive ability in the subgroups. Results: A total of 567 patients who received definitive radiotherapy for ESCC were included in the present study. The optimal cutoff values were 4.5 × 109/L, 3.25, and 220 U/L for neutrophil, neutrophil-to-lymphocyte ratio (NLR), and LDH, respectively. A high level of LDH was significantly associated with advanced N stage (p = 0.031), and neutrophil count was significantly associated with gender (p = 0.001), T stage (p < 0.001), N stage (p = 0.019), clinical stage (p < 0.001), and NLR (p < 0.001). Multivariate survival analysis identified gender (p = 0.006), T stage (p < 0.001), N stage (p = 0.008), treatment modality (p < 0.001), LDH level (p = 0.012), and neutrophil count (p = 0.038) as independent prognostic factors for overall survival. Furthermore, a new prognostic risk scoring (PRS) model based on six prognostic factors was developed, in which the patients were divided into three groups with distinct prognosis (χ2 = 67.94, p < 0.0001). Conclusions: Elevated baseline LDH level and neutrophil count predicted poor prognosis for ESCC patients treated with definitive radiotherapy. A PRS model comprised of LDH, neutrophil count, and other prognostic factors would help identify the patients who would benefit the most from definitive radiotherapy.

Front-line Therapy in Advanced Non-Small Cell Lung Cancer With Sensitive Epidermal Growth Factor Receptor Mutations: A Network Meta-analysis.

PURPOSE: Several epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) were firmly established as front-line treatment for non-small cell lung cancer (NSCLC) that harbored an activating EGFR mutation. Gefitinib or erlotinib was considered the standard of care. TKI-based combination therapy has been investigated and has shown encouraging results. METHODS: The PubMed and EMBASE databases, the Cochrane Central Register of Controlled Trials, and meeting abstracts were screened for relevant studies between January 2000 and February 2019. Prospective randomized controlled trials were included that investigated EGFR TKIs (alone or in combination) in untreated patients with NSCLC whose tumors had sensitive EGFR mutations. A frequentist random effects network meta-analysis model was conducted to assess objective response rate, progression-free survival, and overall survival. P-score was used to rank treatment effects. FINDINGS: Seventeen trials involving 9 treatments and 4373 patients were included. Heterogeneity existed in the network analysis. For progression-free survival, the top 3 treatments were osimertinib, standard of care plus chemotherapy, and standard of care plus bevacizumab; corresponding p-scores were 0.88, 0.79, and 0.75, respectively. For overall survival, the top 3 treatments were standard of care plus chemotherapy, osimertinib, and dacomitinib; corresponding p-scores were 0.89, 0.85, and 0.64. TKI-based combination therapy caused more toxicity than a TKI alone. IMPLICATIONS: Osimertinib seemed to be a better option as upfront therapy for EGFR-mutant NSCLC in terms of efficacy and tolerability.

Impact of sex on the prognosis of patients with esophageal squamous cell cancer underwent definitive radiotherapy: a propensity score-matched analysis.

BACKGROUND: The impact of sex on prognosis of patients with esophageal squamous cell cancer (ESCC) who underwent definitive radiotherapy remained unclear. The present study aimed to determine the impact of sex on the prognosis of patients with ESCC underwent definitive radiotherapy. METHODS: Between January 2009 and December 2015, patients with ESCC underwent definitive radiotherapy in Shantou Central Hospital were included in this study. The Progression-free survival (PFS) and overall survival (OS) rates were estimated using the Kaplan-Meier method. The PFS and OS were compared between female and male patients. The Cox regression model was used to identify prognostic factors. Propensity score-matched analysis was performed to balance baseline characteristics between female and male patients. RESULTS: A total of 683 ESCC patients treated with definitive radiotherapy were included, with 497 male and 186 female patients. In the whole cohort, female patients had a significantly longer median PFS (14.0 months vs 10.6 months, P = 0.0001, HR = 0.688, 95% CI, 0.567-0.836) and OS (20.8 months vs 15.9 months, P = 0.0005, HR = 0.702, 95% CI, 0.575-0.857). In the matched cohort, female patients still had a significantly longer median PFS (13.5 months vs 11.6 months) and OS (19.6 months vs 16.1 months). Multivariate analysis showed that sex was an independent prognostic factor for PFS (HR = 0.746, 95% CI, 0.611-0.910, P = 0.004) and OS (HR = 0.755, 95% CI, 0.615-0.926, P = 0.007). CONCLUSIONS: This present study indicated that sex was an independent prognostic factor in Chinese patients with ESCC underwent definitive radiotherapy, with better survival outcome for women than men. Efforts should be made to investigate the underlying biological mechanism.

First-line checkpoint inhibitors for wild-type advanced non-small-cell cancer: a pair-wise and network meta-analysis.

AIM: To estimate efficacy of checkpoint inhibitors and rank treatment effects in non-small-cell lung cancer. MATERIALS & METHODS: Prospective randomized trials were included. p-score was used to rank treatment effects. RESULTS: A total of nine trials were identified, involving 5504 patients and three checkpoint inhibitors. Pembrolizumab plus chemotherapy had the highest p-score of 0.95 among all the treatments, and was superior to pembrolizumab alone (hazard ratio: 0.87; 95% CI: 0.79-0.95). Combination therapy had more grade 3-5 adverse events; but toxicity-related discontinuation and treatment-related death did not increase. CONCLUSION: Pembrolizumab plus chemotherapy was likely to be the most effective treatment for patients with wild-type advanced NSCLC.

CDK4/6 inhibition versus mTOR blockade as second-line strategy in postmenopausal patients with hormone receptor-positive advanced breast cancer: A network meta-analysis.

BACKGROUND: Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors (palbociclib and abemaciclib) and mammalian target of rapamycin (mTOR) inhibitors (everolimus) are effective agents for restoring endocrine sensitivity in patients with advanced breast cancer progression on prior aromatase inhibitors. We conducted a network meta-analysis to compare these treatments in terms of progression-free survival (PFS), objective response rate (ORR), and clinical benefit rate (CBR). METHODS: The PubMed and Embase databases were searched for relevant publications between January 2000 and June 2018. Treatments were ranked based on a network meta-analysis. Ranking was determined by P-score. A random-effect model was used when heterogeneity was detected; otherwise, a fixed-effect model was used. RESULTS: Six trials comprising 4063 patients formed the comparison network. Compared with everolimus plus exemestane, the combinations of palbociclib or abemaciclib with fulvestrant showed similar efficacies in PFS and no differences in ORR. For the CBR, palbociclib demonstrated improvement, while abemaciclib did not. Incidences of severe adverse events did not significantly differ. A total of 29%, 15.9%, and 4% of patients discontinued everolimus, abemaciclib, and palbociclib, respectively, due to toxicity. CONCLUSION: These results suggest similar efficacies between CDK4/6 inhibition and mTOR blockade; however, CDK4/6 inhibitors were associated with favorable toxicity profiles.

Definitive chemoradiation therapy or surgery for clinical T1-3N0-1M0 thoracic esophageal squamous cell carcinoma: A propensity score matching analysis.

BACKGROUND: To compare overall survival in patients with clinical T1-3N0-1 thoracic esophageal squamous cell carcinoma treated with surgery or definitive chemoradiation therapy (CRT). METHODS: We used propensity-score matching to derive 1:1 cohorts of surgery versus definitive CRT. Statistical analysis was performed using χ2 or Fisher's exact tests. Survival functions were estimated using Kaplan-Meier survival plots, and survival distributions were compared using log-rank tests. Cox proportional hazards modeling was used to analyze the factors affecting overall survival. RESULTS: A total of 334 patients treated with surgery and 252 treated with definitive CRT were included. 129 (38.6%) of 334 patients had recurrence after surgery versus 118 (46.8%) of 252 after definitive CRT. Before matching, the median overall survival were 39.5 months (95% CI, 28.8-50.2) and 23.5 months (95% CI, 18.5-28.5) (P < 0.001) in the surgery and definitive CRT group, respectively. After matching (112 patients in each treatment group), median overall survival was 43.6 months (95% CI, 28.1-59.1) with surgery versus 19.3 months (95% CI, 14.4-24.2) with CRT (P < 0.001). CONCLUSIONS: In this retrospective analysis, surgery was associated with better overall survival compared with definitive CRT.

Preoperative Administration of Olive Oil Reduces Chylothorax After Minimally Invasive Esophagectomy.

BACKGROUND: Chylothorax after esophagectomy is uncommon but potentially fatal. We performed a retrospective study to assess the effect of olive oil administered orally before surgery on reducing chylothorax in patients who underwent minimal invasive esophagectomy. METHODS: Between May 2013 and December 2016, patients with esophageal squamous cell cancer who underwent minimal invasive esophagectomy were screened. Patients in the investigational group were preoperatively administered olive oil orally 8 hours before surgery, and patients in the control arm received no olive oil. We used a propensity score matching model to derive 1:1 cohorts. Statistical analysis was performed by using the t test or χ2 or Fisher's exact test. RESULTS: The propensity score matching model finally selected 384 of 425 patients, with 192 patients in each group. The patient characteristics were balanced. Oral olive oil was well tolerated. The thoracic duct identification rate was higher in the investigational group (100% versus 45.31%, χ2 = 141.78, p < 0.01). The investigational group was associated with a reduced incidence of ligation (7.81% versus 18.22%, χ2 = 8.03, p = 0.003). The incidence of chylothorax was significantly reduced in the investigational group compared with that of the control group (0% versus 3.12%, χ2 = 4.23, p = 0.03). CONCLUSIONS: Preoperative administration of olive oil is a simple and safe method to minimize chylothorax complicating minimal invasive esophagectomy.

A network meta-analysis of nonsmall-cell lung cancer patients with an activating EGFR mutation: Should osimertinib be the first-line treatment?

BACKGROUND: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are the preferred first-line treatment for nonsmall-cell lung cancer (NSCLC) patients with an activating EGFR mutation. Osimertinib, compared with erlotinib or gefitinib, showed an improvement in progression-free survival (PFS) in a recent trial. The authors compared EGFR TKIs in terms of PFS in a network meta-analysis. METHODS: The PubMed and Embase databases and meeting abstracts were screened for relevant studies between January 2009 and November 2017. A random-effect frequentist network meta-analysis model was conducted to assess PFS. P-score was used to rank treatment effects. RESULTS: Eleven trials with 3145 patients and 5 TKIs (gefitinib, erlotinib, afatinib, dacomitinib, and osimertinib) were included. Heterogeneity and inconsistency existed in the network analysis. Gefitinib and erlotinib had similar effects (hazard ratio [HR] 0.94, 95% confidence interval [CI] 0.76-1.15). For all patients, the 3 TKIs with the highest probability of benefit were osimertinib, dacomitinib, and afatinib, with P-scores of 91%, 78%, and 46%, respectively. Compared with erlotinib or gefitinib, osimertinib was associated with improvement in men (HR = 0.79, 95% CI, 0.68-0.92), non-Asians (HR = 0.63, 95% CI, 0.40-0.98), smokers (HR = 0.73, 95% CI, 0.56-0.95), and those with a Del19 mutation (HR = 0.69, 95% CI, 0.54-0.90); dacomitinib and afatinib showed no improvement. Toxicity profiles mostly overlapped in all the EGFR TKIs. Toxicity-related death was rare. CONCLUSIONS: Osimertinib was shown to be the best agent to achieve the longest PFS in NSCLC patients with an activating EGFR mutation. However, the benefit of osimertinib might be restricted to certain subgroups.

Effect of consolidation chemotherapy following definitive chemoradiotherapy in patients with esophageal squamous cell cancer.

Definitive chemoradiotherapy (dCRT) is a treatment option for patients with localized esophageal squamous cell carcinoma (ESCC). We investigated consolidation chemotherapy (CCT) in patients with ESCC who attained clinical complete response after dCRT. Between January 2009 and December 2012, medical records of ESCC patients treated with dCRT were retrospectively reviewed, and those who attained CCR were identified. Progression-free survival and overall survival rates were estimated by the Kaplan-Meier method. The Cox regression model was used to determine prognostic factors. Of the 522 patients treated with dCRT, 209 patients achieved CCR, with 67 receiving consolidation chemotherapy (the CCT group) and 142 receiving dCRT alone (the control group). CCT did not prolong progression-free survival (33.0 vs 18.0 months, P = 0.07, HR = 0.70, 95% CI, 0.48-1.04); however, CCT improved the median overall survival (53.4 vs 27.0 months, P = 0.04, HR = 0.67, 95% CI, 0.44-0.99) compared with dCRT alone. CCT remained a favorable prognostic factor for overall survival in a multivariate analysis (HR = 0.59, P = 0.02); however, a propensity score analysis failed to show an additional overall survival benefit with CCT. In the present analysis, CCT did not improve progression-free survival but may have extended overall survival in ESCC patients who achieved complete clinical response after dCRT.

Fulvestrant plus targeted agents versus fulvestrant alone for treatment of hormone-receptor positive advanced breast cancer progressed on previous endocrine therapy: a meta-analysis of randomized controlled trials.

To compare the addition of targeted agents to fulvestrant with fulvestrant alone in hormone-receptor positive advanced breast cancer progressed on previous endocrine therapy; a meta-analysis of all relevant randomized controlled trials was performed. The PubMed, Embase databases and the Cochrane Central Register of Controlled Trials were searched for relevant publications reporting randomized controlled trials between January 2000 and June 2016. Progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and toxicity were assessed. Eight trials with a total of 2,470 patients were included in this meta-analysis. Compared with fulvestrant alone, combination therapy improved PFS (HR = 0.79; 95% CI 0.72-0.87; P = 0.00), increased ORR (RR = 1.70; 95% CI 1.30-2.21; P = 0.00), and showed a trend of increase in DCR (RR = 1.27; 95% CI 0.96-1.69, P = 0.09). In network analysis, only CD4/6 and PI3K/m-TOR inhibitors showed significant treatment effects with a P-score of 0.9999 and 0.7615, respectively. Patients treated with combination therapy developed more grade 3 or greater toxic effects (RR = 1.24; 95% CI 1.13-1.36; P = 0.00). Combining targeted agents with fulvestrant showed benefit but with increased toxicity in patients with advanced breast cancer compared with fulvestrant alone. Biomarkers for treatment optimization are lacking. The CD4/6 and PI3K/m-TOR pathways merit further investigation.

Capecitabine in Combination with Standard (Neo)Adjuvant Regimens in Early Breast Cancer: Survival Outcome from a Meta-Analysis of Randomized Controlled Trials.

Capecitabine has been investigated in early breast cancer in several studies, but it was undefined that whether it could improve survival. To investigate whether the addition of capecitabine affected survival in patients with early breast cancer, a meta-analysis was conducted and overall survival (OS), disease-free survival (DFS), and toxicity were assessed. The PubMed, Embase databases and the Cochrane Central Register of Controlled Trials were searched for studies between January 2006 and April 2016. Hazard ratios (HRs) with their 95% confidence intervals (CIs), or data for calculating HRs with 95% CI were derived. Seven trials with 9097 patients, consisted of 4 adjuvant and 3 neoadjuvant studies, were included in this meta-analysis. Adding capecitabine showed no improvement in DFS (HR = 0.93; 95% CI, 0.85-1.02; P = 0.12), whereas a significant improvement in OS was observed (HR = 0.85; 95% CI, 0.75-0.96; P = 0.008). A sub-analysis of DFS showed that benefit of capecitabine derived from patients with triple negative subtype and with extensive axillary involvement. Safety profiles were consistent with the known side-effects of capecitabine, but more patients discontinued scheduled treatment in the capecitabine group. Combining capecitabine with standard (neo)adjuvant regimens in early breast cancer demonstrated a significantly superior OS, and indicated DFS improvement in some subtypes with high risk of recurrence. Selection of subtypes was a key to identify patients who might gain survival benefit from capecitabine.