Robotic Versus Conventional Minimally Invasive Esophagectomy for Esophageal Cancer: A Meta-analysis.

OBJECTIVES: To give a comprehensive review of the literature comparing perioperative outcomes and long-term survival with robotic-assisted minimally invasive esophagectomy (RAMIE) versus minimally invasive esophagectomy (MIE) for esophageal cancer. BACKGROUND: Curative minimally invasive surgical treatment for esophageal cancer includes RAMIE and conventional MIE. It remains controversial whether RAMIE is comparable to MIE. METHODS: This review was registered at the International Prospective Register of Systematic Reviews (CRD42021260963). A systematic search of databases was conducted. Perioperative outcomes and long-term survival were analyzed and subgroup analysis was conducted. Cumulative meta-analysis was performed to track therapeutic effectiveness. RESULTS: Eighteen studies were included and a total of 2932 patients (92.88% squamous cell carcinoma, 29.83% neoadjuvant therapy, and 38.93% stage III-IV), 1418 underwent RAMIE and 1514 underwent MIE, were analyzed. The number of total lymph nodes (LNs) [23.35 (95% CI: 21.41-25.29) vs 21.98 (95% CI: 20.31-23.65); mean difference (MD) = 1.18; 95% CI: 0.06-2.30; P =0.04], abdominal LNs [9.05 (95% CI: 8.16-9.94) vs 7.75 (95% CI: 6.62-8.88); MD = 1.04; 95% CI: 0.19-1.89; P =0.02] and LNs along the left recurrent laryngeal nerve [1.74 (95% CI: 1.04-2.43) vs 1.34 (95% CI: 0.32-2.35); MD = 0.22; 95% CI: 0.09-0.35; P <0.001] were significantly higher in the RAMIE group. RAMIE is associated with a lower incidence of pneumonia [9.61% (95% CI: 7.38%-11.84%) vs 14.74% (95% CI: 11.62%-18.15%); odds ratio = 0.73; 95% CI: 0.58-0.93; P =0.01]. Meanwhile, other perioperative outcomes, such as operative time, blood loss, length of hospital stay, 30/90-day mortality, and R0 resection, showed no significant difference between the two groups. Regarding long-term survival, the 3-year overall survival was similar in the two groups, whereas patients undergoing RAMIE had a higher rate of 3-year disease-free survival compared with the MIE group [77.98% (95% CI: 72.77%-82.43%) vs 70.65% (95% CI: 63.87%-77.00%); odds ratio = 1.42; 95% CI: 1.11-1.83; P =0.006]. A cumulative meta-analysis conducted for each outcome demonstrated relatively stable effects in the two groups. Analyses of each subgroup showed similar overall outcomes. CONCLUSIONS: RAMIE is a safe and feasible alternative to MIE in the treatment of resectable esophageal cancer with comparable perioperative outcomes and seems to indicate a possible superiority in LNs dissection in the abdominal cavity, and LNs dissected along the left recurrent laryngeal nerve and 3-year disease-free survival in particular in esophageal squamous cell carcinoma. Further randomized studies are needed to better evaluate the long-term benefits of RAMIE compared with MIE.

Lymph Node Ratio Improves Prediction of Overall Survival in Esophageal Cancer Patients Receiving Neoadjuvant Chemoradiotherapy: A National Cancer Database Analysis.

OBJECTIVE: This study aimed to propose a revised ypN (r-ypN) classification based on lymph node ratio (LNR) and to examine its prognostic value in postneoadjuvant esophageal cancer. BACKGROUND: A new postneoadjuvant pathologic (ypTNM) staging classification has been introduced for esophageal cancer. However, the ypN classification currently defined by the number of positive lymph nodes is influenced by the extent of lymphadenectomy. METHODS: Data on 7195 esophageal cancer patients receiving neoadjuvant chemoradiation were extracted from the National Cancer Database (NCDB). Four r-ypN stages were defined by 3 LNR thresholds (0%, 10%, and 20% using X-tile software). A revised ypTNM (r-ypTNM) classification was developed by solely changing N categories. Kaplan-Meier method and Cox proportional hazards models were used for survival analyses. Akaike information criterion (AIC) and Harrell's concordance index ( C -index) were used to compare the predictive performance of the current and the revised classification. External validation was performed using an independent cohort from the NEOCRTEC5010 clinical trial. RESULTS: Both ypN ( P <0.001) and r-ypN ( P <0.001) were independent prognostic factors of overall survival (OS) for esophageal cancer patients. Kaplan-Meier curves demonstrated a better discrimination with r-ypN than ypN categories. Within each ypN category (except ypN3), OS was significantly different comparing r-ypN strata; however, there were no differences between ypN strata within each r-ypN category (except r-ypN3). r-ypN (AIC: 60752 vs 60782; C -index: 0.591 vs 0.587) and r-ypTNM (AIC: 60623 vs 60628; C -index: 0.613 vs 0.610) showed better predictive performance than the current staging system, with a lower AIC (better calibration) and higher C -index (improved discrimination). This advantage was also confirmed by external validation using the NEOCRTEC5010 cohort. CONCLUSIONS: LNR showed better performance than ypN in predicting OS of esophageal cancer patients after neoadjuvant chemoradiation and may be an improvement on the current staging system.

Robotic-assisted Versus Video-assisted Thoracoscopic Lobectomy: Short-term Results of a Randomized Clinical Trial (RVlob Trial).

OBJECTIVE: To determine whether RAL affects perioperative outcomes and long-term efficacy in NSCLC patients, compared with traditional VAL. SUMMARY OF BACKGROUND DATA: RAL is a promising treatment for NSCLC. However, its efficacy has not been fully evaluated. METHODS: A single-center, open-labeled prospective randomized clinical trial was launched in May 2017 to compare the efficacy of RAL and VAL. By May 2020, 320 patients were enrolled. The perioperative results of RAL and VAL were compared. RESULTS: The 320 enrolled patients were randomly assigned to the RAL group (n = 157) and the VAL group (n = 163). Perioperative outcomes were comparable between the 2 groups, including the length of hospital stay (P = 0.76) and the rate of postoperative complications (P = 0.45). No perioperative mortality occurred in either group. The total amount of chest tube drainage {830 mL [interquartile range (IQR), 550-1130 mL] vs 685 mL [IQR, 367.5-1160 mL], P = 0.007} and hospitalization costs [$12821 (IQR, $12145-$13924) vs $8009 (IQR, $7014-$9003), P < 0.001] were significantly higher in the RAL group. RAL group had a significantly higher number of LNs harvested [11 (IQR, 8-15) vs 10 (IQR, 8-13), P = 0.02], higher number of N1 LNs [6 (IQR, 4-8) vs 5 (IQR, 3-7), P = 0.005], and more LN stations examined [6 (IQR, 5-7) vs 5 (IQR, 4-6), P < 0.001]. CONCLUSIONS: Both RAL and VAL are safe and feasible for the treatment of NSCLC. RAL achieved similar perioperative outcomes, together with higher LN yield. Further follow-up investigations are required to evaluate the long-term efficacy of RAL. (ClinicalTrials.gov identifier: NCT03134534).

Effects of pre-operative enteral immunonutrition for esophageal cancer patients treated with neoadjuvant chemoradiotherapy: protocol for a multicenter randomized controlled trial (point trial, pre-operative immunonutrition therapy).

BACKGROUND: Neoadjuvant chemoradiation followed by esophagectomy has been established as the first-line treatment for locally advanced esophageal cancer. Postoperative enteral nutrition has been widely used to improve perioperative outcomes. However, whether to implement preoperative nutritional intervention during neoadjuvant therapy is yet to be verified by prospective studies. METHODS: POINT trial is a multicenter, open-labeled, randomized controlled trial. A total of 244 patients with surgically resectable esophageal cancer are randomly assigned to nutritional therapy group (arm A) or control group (arm B) with a 2:1 ratio. Both groups receive neoadjuvant chemotherapy with concurrent radiotherapy based on the CROSS regimen followed by minimally invasive esophagectomy. The primary endpoint is the rate of nutrition and immune-related complications after surgery. Secondary endpoints include completion rate of neoadjuvant chemoradiation and related adverse events, rate of pathological complete response, perioperative outcomes, nutritional status, overall survival, progression-free survival and quality of life. DISCUSSION: This trial aims to verify whether immunonutrition during neoadjuvant chemoradiation can reduce the rate of complications and improve perioperative outcomes. Frequent communication and monitoring are essential for a multicenter investigator-initiated trial. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04513418. The trial was prospectively registered on 14 August 2020, https://www. CLINICALTRIALS: gov/ct2/show/NCT04513418 .

Effects of preoperative nutrition on postoperative outcomes in esophageal cancer: a systematic review and meta-analysis.

Postoperative enteral nutrition has been widely implemented in esophageal cancer, but the efficacy and safety of preoperative nutrition, particularly immune-enhancing nutrition (IEN), remain controversial. This meta-analysis aims to provide a quantitative synthesis of whether preoperative nutrition improves postoperative morbidity and mortality in patients with resectable esophageal cancer. A systematic search was conducted in Medline, Embase, Cochrane, and databases of clinical trials dated up to December 2019. Randomized controlled trials and observational studies comparing postoperative outcomes between esophageal cancer patients with and without preoperative nutritional support were included. Random-effects model was applied in the meta-analysis of primary outcomes (overall complication rate, in-hospital mortality) and secondary outcomes (infectious complication rate, anastomotic leak rate, length of postoperative hospital stay). Complications of feeding tube access and perioperative weight loss were evaluated by qualitative synthesis. Subgroup analyses were performed by stratifying immunonutrition and standard nutrition before surgery. Subgroup analysis of randomized controlled trials alone was also done. A total of 15 studies enrolling 1864 participants were included. The overall meta-analysis found that preoperative nutrition could reduce infectious complications (odds ratio [OR] = 0.51, 95% confidence interval [CI] [0.26, 0.98]; I2 = 48%) and length of hospital stay (mean difference = -2.10 day, 95% CI [-3.72, -0.47]; I2 = 78%) after esophagectomy, whereas no significant difference was revealed in the incidence of overall complications (OR = 0.76, 95% CI [0.52, 1.11]; I2 = 32%), in-hospital mortality (OR = 1.03, 95% CI [0.41, 2.61]; I2 = 12%), and anastomotic leak (OR = 1.05, 95% CI [0.69, 1.58]; I2 = 0%). Subgroup of preoperative immunonutrition showed more prominent benefits. The complication rate of feeding tube access was low (1.6-16%). In conclusion, preoperative nutrition is safe in esophageal cancer, but benefits are observed in infectious complication rate and length of stay on a limited scale. IEN holds more advantages over standard nutrition. Randomized trials in the context of nutritional support during neoadjuvant therapy are in demand.

A combination model of AD biomarkers revealed by machine learning precisely predicts Alzheimer's dementia: China Aging and Neurodegenerative Initiative (CANDI) study.

INTRODUCTION: To test the utility of the "A/T/N" system in the Chinese population, we study core Alzheimer's disease (AD) biomarkers in a newly established Chinese cohort. METHODS: A total of 411 participants were selected, including 96 cognitively normal individuals, 94 patients with mild cognitive impairment (MCI) patients, 173 patients with AD, and 48 patients with non-AD dementia. Fluid biomarkers were measured with single molecule array. Amyloid beta (Aß) deposition was determined by 18 F-Flobetapir positron emission tomography (PET), and brain atrophy was quantified using magnetic resonance imaging (MRI). RESULTS: Aß42/Aß40 was decreased, whereas levels of phosphorylated tau (p-tau) were increased in cerebrospinal fluid (CSF) and plasma from patients with AD. CSF Aß42/Aß40, CSF p-tau, and plasma p-tau showed a high concordance in discriminating between AD and non-AD dementia or elderly controls. A combination of plasma p-tau, apolipoprotein E (APOE) genotype, and MRI measures accurately predicted amyloid PET status. DISCUSSION: These results revealed a universal applicability of the "A/T/N" framework in a Chinese population and established an optimal diagnostic model consisting of cost-effective and non-invasive approaches for diagnosing AD.

Hsp40 Protein DNAJB6 Interacts with Viral NS3 and Inhibits the Replication of the Japanese Encephalitis Virus.

The Japanese encephalitis virus (JEV) is a mosquito-borne flavivirus prevalent in east and southeast Asia, the Western Pacific, and northern Australia. Since viruses are obligatory intracellular pathogens, the dynamic processes of viral entry, replication, and assembly are dependent on numerous host-pathogen interactions. Efforts to identify JEV-interacting host factors are ongoing because their identification and characterization remain incomplete. Three enzymatic activities of flavivirus non-structural protein 3 (NS3), including serine protease, RNA helicase, and triphosphatase, play major roles in the flaviviruses lifecycle. To identify cellular factors that interact with NS3, we screened a human brain cDNA library using a yeast two-hybrid assay, and identified eight proteins that putatively interact with NS3: COPS5, FBLN5, PPP2CB, CRBN, DNAJB6, UBE2N, ZNF350, and GPR137B. We demonstrated that the DnaJ heat shock protein family (Hsp40) member B6 (DNAJB6) colocalizes and interacts with NS3, and has a negative regulatory function in JEV replication. We also show that loss of DNAJB6 function results in significantly increased viral replication, but does not affect viral binding or internalization. Moreover, the time-course of DNAJB6 disruption during JEV infection varies in a viral load-dependent manner, suggesting that JEV targets this host chaperone protein for viral benefit. Deciphering the modes of NS3-interacting host proteins functions in virion production will shed light on JEV pathogenic mechanisms and may also reveal new avenues for antiviral therapeutics.

Ultra-short-period perioperative pulmonary rehabilitation on short-term outcomes after surgery in smoking patients with lung cancer: A randomized clinical trial.

BACKGROUND: Pulmonary rehabilitation is essential for airway management after thoracic surgery. Most current pulmonary rehabilitations are composed of 2-4-week exercises, which require significant consumption of medical resources and concerns about disease progression. MATERIALS AND METHODS: This single-center, prospective, randomized controlled trial enrolled smoking patients with pulmonary masses or nodules suitable for lobectomy, aged 18-80, with smoking history (≥20 pack-years). Eligible patients were randomized in a 1:1 ratio into two groups. Patients in the intervention group underwent perioperative breathing exercises based on positive pressure vibration expectoration and three-day preoperative lower limb endurance training. Patients in the control group received routine perioperative care. The primary outcome was in-hospital incidence of postoperative pulmonary complications. Secondary outcomes included postoperative hospital stay, total hospitalization cost, postoperative drainage time, drainage volume, semiquantitative cough strength score, pain score, Borg scale-assessed fatigue, and walking distance on postoperative days 1 and 2. RESULTS: A total of 194 patients were included in the study with 94 in the intervention group and 100 in the control group. Our ultrashort pulmonary rehabilitation program potentially reduced pulmonary complications incidence (24.5% vs. 33.0%), but without statistical significance (P=0.190). No significant differences were found in other perioperative outcomes, except for postoperative semiquantitative cough strength score (3 [interquartile range, 3-3.75] vs. 3 [interquartile range, 2-3], P<0.001) and change in walking distance from postoperative days 1 to 2 (60 [interquartile range, 40-82.5] vs. 30 [interquartile range, 10-60], P=0.003). CONCLUSION: There were no significant differences in postoperative complications and other hospitalizations, but our ultrashort rehabilitation program improved patients' semiquantitative cough strength score and walking distance, indicating potential for better outcomes. This treatment is a safe and effective means of airway management for thoracic surgery in the era of enhanced recovery. (ClinicalTrials.gov Identifier: XXX).

Immune microenvironment heterogeneity of concurrent adenocarcinoma and squamous cell carcinoma in multiple primary lung cancers.

The molecular profiles and tumor immune microenvironment (TIME) of multiple primary lung cancers (MPLCs) presenting as concurrent lung adenocarcinoma (ADC) and squamous cell carcinoma (SQCC) remain unknown. We aimed to clarify these factors. We performed whole-exome sequencing (WES), RNA sequencing (RNA-Seq), and multiplex immunohistochemistry (mIHC) for five patients with concurrent ADC and SQCC. We found the genetic mutations were similar between ADC and SQCC groups. RNA-Seq revealed that the gene expression and pathways enriched in ADC and SQCC groups were quite different. Gene set enrichment analysis (GSVA) showed that nine gene sets were significantly differentially expressed between the ADC and SQCC groups (p < 0.05), with four gene sets relevant to squamous cell features upregulated in the SQCC group and five gene sets upregulated in the ADC group. Reactome enrichment analysis of differentially expressed genes showed that the immune function-related pathways, including programmed cell death, innate immune system, interleukin-12 family signaling, and toll-like receptor 2/4 pathways, etc. were significantly enriched. Transcriptomic TIME analysis, with mIHC in patient specimens and in vivo validation, showed tumor-infiltrating immune cells were significantly more enriched and diverse in ADC, especially CD8 + T cells. Our results revealed that the transcriptomic profiles and TIME features were quite different between ADC and SQCC lesions. ADC lesions exhibited a more active TIME than SQCC lesions in MPLCs.

Lymph node metastasis in early invasive lung adenocarcinoma: Prediction model establishment and validation based on genomic profiling and clinicopathologic characteristics.

BACKGROUND: The presence of lymph node (LN) metastasis directly affects the treatment strategy for lung adenocarcinoma (LUAD). Next-generation sequencing (NGS) has been widely used in patients with advanced LUAD to identify targeted genes, while early detection of pathologic LN metastasis using NGS has not been assessed. METHODS: Clinicopathologic features and molecular characteristics of 224 patients from Ruijin Hospital were analyzed to detect factors associated with LN metastases. Another 140 patients from Huashan Hospital were set as a test cohort. RESULTS: Twenty-four out of 224 patients were found to have lymph node metastases (10.7%). Pathologic LN-positive tumors showed higher mutant allele tumor heterogeneity (p < 0.05), higher tumor mutation burden (p < 0.001), as well as more frequent KEAP1 (p = 0.001), STK11 (p = 0.004), KRAS (p = 0.007), CTNNB1 (p = 0.017), TP53, and ARID2 mutations (both p = 0.02); whereas low frequency of EGFR mutation (p = 0.005). A predictive nomogram involving male sex, solid tumor morphology, higher T stage, EGFR wild-type, and TP53, STK11, CDKN2A, KEAP1, ARID2, KRAS, SDHA, SPEN, CTNNB1, DICER1 mutations showed outstanding efficiency in both the training cohort (AUC = 0.819) and the test cohort (AUC = 0.780). CONCLUSION: This study suggests that the integration of genomic profiling and clinical features identifies early-invasive LUAD patients at higher risk of LN metastasis. Improved identification of LN metastasis is beneficial for the optimization of the patient's therapy decisions.

Online tools to predict individualised survival for primary oesophageal cancer patients with and without pathological complete response after neoadjuvant therapy followed by oesophagectomy: development and external validation of two independent nomograms.

OBJECTIVE: This study aimed to develop and validate robust predictive models for patients with oesophageal cancer who achieved a pathological complete response (pCR) and those who did not (non-pCR) after neoadjuvant therapy and oesophagectomy. DESIGN: Clinicopathological data of 6517 primary oesophageal cancer patients who underwent neoadjuvant therapy and oesophagectomy were obtained from the National Cancer Database for the training cohort. An independent cohort of 444 Chinese patients served as the validation set. Two distinct multivariable Cox models of overall survival (OS) were constructed for pCR and non-pCR patients, respectively, and were presented using web-based dynamic nomograms (graphical representation of predicted OS based on the clinical characteristics that a patient could input into the website). The calibration plot, concordance index and decision curve analysis were employed to assess calibration, discrimination and clinical usefulness of the predictive models. RESULTS: In total, 13 and 15 variables were used to predict OS for pCR and non-pCR patients undergoing neoadjuvant therapy followed by oesophagectomy, respectively. Key predictors included demographic characteristics, pretreatment clinical stage, surgical approach, pathological information and postoperative treatments. The predictive models for pCR and non-pCR patients demonstrated good calibration and clinical utility, with acceptable discrimination that surpassed that of the current tumour, node, metastases staging system. CONCLUSIONS: The web-based dynamic nomograms for pCR (https://predict-survival.shinyapps.io/pCR-eso/) and non-pCR patients (https://predict-survival.shinyapps.io/non-pCR-eso/) developed in this study can facilitate the calculation of OS probability for individual patients undergoing neoadjuvant therapy and radical oesophagectomy, aiding clinicians and patients in making personalised treatment decisions.

Subjective and Objective Audio-Visual Quality Assessment for User Generated Content.

In recent years, User Generated Content (UGC) has grown dramatically in video sharing applications. It is necessary for service-providers to use video quality assessment (VQA) to monitor and control users' Quality of Experience when watching UGC videos. However, most existing UGC VQA studies only focus on the visual distortions of videos, ignoring that the perceptual quality also depends on the accompanying audio signals. In this paper, we conduct a comprehensive study on UGC audio-visual quality assessment (AVQA) from both subjective and objective perspectives. Specially, we construct the first UGC AVQA database named SJTU-UAV database, which includes 520 in-the-wild UGC audio and video (A/V) sequences collected from the YFCC100m database. A subjective AVQA experiment is conducted on the database to obtain the mean opinion scores (MOSs) of the A/V sequences. To demonstrate the content diversity of the SJTU-UAV database, we give a detailed analysis of the SJTU-UAV database as well as other two synthetically-distorted AVQA databases and one authentically-distorted VQA database, from both the audio and video aspects. Then, to facilitate the development of AVQA fields, we construct a benchmark of AVQA models on the proposed SJTU-UAV database and other two AVQA databases, of which the benchmark models consist of AVQA models designed for synthetically distorted A/V sequences and AVQA models built through combining the popular VQA methods and audio features via support vector regressor (SVR). Finally, considering benchmark AVQA models perform poorly in assessing in-the-wild UGC videos, we further propose an effective AVQA model via jointly learning quality-aware audio and visual feature representations in the temporal domain, which is seldom investigated by existing AVQA models. Our proposed model outperforms the aforementioned benchmark AVQA models on the SJTU-UAV database and two synthetically distorted AVQA databases. The SJTU-UAV database and the code of the proposed model will be released to facilitate further research.

Attention-Guided Neural Networks for Full-Reference and No-Reference Audio-Visual Quality Assessment.

With the popularity of mobile Internet, audio and video (A/V) have become the main way for people to entertain and socialize daily. However, in order to reduce the cost of media storage and transmission, A/V signals will be compressed by service providers before they are transmitted to end-users, which inevitably causes distortions in the A/V signals and degrades the end-user's Quality of Experience (QoE). This motivates us to research the objective audio-visual quality assessment (AVQA). In the field of AVQA, most previous works only focus on single-mode audio or visual signals, which ignores that the perceptual quality of users depends on both audio and video signals. Therefore, we propose an objective AVQA architecture for multi-mode signals based on attentional neural networks. Specifically, we first utilize an attention prediction model to extract the salient regions of video frames. Then, a pre-trained convolutional neural network is used to extract short-time features of the salient regions and the corresponding audio signals. Next, the short-time features are fed into Gated Recurrent Unit (GRU) networks to model the temporal relationship between adjacent frames. Finally, the fully connected layers are utilized to fuse the temporal related features of A/V signals modeled by the GRU network into the final quality score. The proposed architecture is flexible and can be applied to both full-reference and no-reference AVQA. Experimental results on the LIVE-SJTU Database and UnB-AVC Database demonstrate that our model outperforms the state-of-the-art AVQA methods. The code of the proposed method will be publicly available to promote the development of the field of AVQA.

Correlation of blood-brain barrier leakage with cerebral small vessel disease including cerebral microbleeds in Alzheimer's disease.

Background: Blood-brain barrier (BBB) damage is considered an important part of Alzheimer's disease (AD) progression, and cerebral small-vessel disease (CSVD) is commonly associated with AD. However, the relationship between BBB damage, small cerebrovascular lesions, especially cerebral microbleeds (CMBs), and amyloid and tau biomarkers remains controversial. Therefore, our study aimed to further investigate their association in our cohort of patients with AD. Methods: A total of 139 individuals were divided into probable AD (18F-florbetapir PET positive, n = 101) and control group (cognitively normal, n = 38). The levels of cerebrospinal fluid (CSF) and plasma t-tau, p-tau181, Aß40, Aß42, and albumin were measured using corresponding commercial assay kits, and the CSF/plasma albumin ratio (Qalb), an indicator of BBB dysfunction, was calculated. CSVD burden and the number of CMBs were defined using magnetic resonance imaging. Results: Patients with AD had higher Qalb (p = 0.0024), higher numbers of CMBs (p = 0.03), and greater CSVD burden (p < 0.0001). In the AD group, CMBs and CSVD correlated with a higher Qalb (p = 0.03), and the numbers of CMBs negatively correlated with CSF Aß42 (p = 0.02). Conclusion: Blood-brain barrier damage was accompanied by a more severe burden of CSVD, including CMB, in patients with AD.

Health-Related Quality of Life Following Robotic-Assisted or Video-Assisted Lobectomy in Patients With Non-Small Cell Lung Cancer: Results From the RVlob Randomized Clinical Trial.

BACKGROUND: Robot-assisted lobectomy (RAL) is increasingly used as an alternative to video-assisted lobectomy (VAL) for resectable non-small cell lung cancer (NSCLC). However, there is little evidence of any difference in postoperative health-related quality of life (HRQoL) between these two approaches. RESEARCH QUESTION: Is RAL superior to VAL in improving quality of life in patients with resectable NSCLC? STUDY DESIGN AND METHODS: We performed a single-center, open-label randomized clinical trial from May 2017 to May 2020 with 320 enrolled patients undergoing RAL or VAL for resectable NSCLC (RVlob trial; NCT03134534). Postoperative pain was evaluated by visual analog score or numeric rating score on postoperative day 1 and at weeks 4, 24, and 48. The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life Questionnaire (QLQ-C30), EORTC Quality of Life Questionnaire in Lung Cancer (QLQ-LC13), and the European Quality of Life 5 Dimensions (EQ-5D) questionnaire were also administered at weeks 4, 24, and 48 after surgery. RESULTS: One hundred and fifty-seven patients underwent RAL and 163 underwent VAL. The mean pain score of patients after RAL was significantly lower at week 4 (2.097 ± 0.111 vs 2.431 ± 0.108; P = .032). QLQ-C30 and QLQ-LC13 summary scores (P > .05) were similar for both RAL and VAL during the first 48 weeks of follow-up. HRQoL scores assessed with the EQ-5D questionnaire were also comparable between the two groups (P > .05) during the whole study period. INTERPRETATION: Both RAL and VAL showed satisfactory and comparable HRQoL and postoperative pain up to 48 weeks after surgery, despite some minor statistical differences at week 4. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov; No.: NCT03134534; URL: www. CLINICALTRIALS: gov.

Preparation Process Optimization of Peptides from Agaricus blazei Murrill, and Comparison of Their Antioxidant and Immune-Enhancing Activities Separated by Ultrafiltration Membrane Technology.

Agaricus blazei murrill (ABM), a large fungus, is reported to have extensive biological activities but the antioxidant and immune-regulatory capacities have been less studied and the components responsible for the functions are unclear. This study prepared ABM peptides (ABMP) using ultrasound-assisted enzymatic extraction (UAEE) strategy and cascade ultrafiltration (UF) membrane technology. The UAEE extraction conditions were optimized using response surface methodology (RSM) with four factors and three levels to achieve the maximum ABMP yield (34.03%); the optimal conditions were an enzyme amount of 4%, ratio of ABM to water of 1:30, ultrasonic power of 360 W, and ultrasonic time of 30 min. Four ABMP fractions were obtained after UF with different pore size and their antioxidant and immune-regulatory abilities were evaluated and compared. The results showed that they could effectively scavenge DPPH, hydroxyl, and ABTS radicals, especially for ABMP-2; the scavenging rate of the above radicals were 79.31%, 63.60%, and 96.08%, respectively. In addition, four ABMP fractions also activated macrophage activity through strengthening phagocytosis and the production of NO, IL-6, IL-1ß, and TNF-α in a dose-dependent manner. Notably, the ABMP-2 fraction with a MW of 3-5 kDa and peptide purity of 82.88% was found to have the best effect, showing the maximum phagocytosis (189.37%) as well as NO (7.98 µM), IL-6 (195.05 pg/mL), IL-1ß (876.15 pg/mL), and TNF-α (1620 pg/mL) secretion at a treatment concentration of 150 µg/mL. The findings indicated that the ABMP, especially for the separate ABMP-2, could be used as dietary supplements and have the potential to be exploited as immune-enhancing agents.

Robot-assisted Ivor Lewis Esophagectomy (RAILE): A review of surgical techniques and clinical outcomes.

In the past 20 years, robotic system has gradually found a place in esophagectomy which is a demanding procedure in the deep and narrow thoracic cavity containing crucial functional structures. Ivor Lewis esophagectomy (ILE) is a mainstream surgery type for esophagectomy and is widely accepted for its capability in lymphadenectomy and relatively mitigated trauma. As a minimally invasive technique, robot-assisted Ivor Lewis esophagectomy (RAILE) has been frequently compared with the video-assisted procedure and the traditional open procedure. However, high-quality evidence elucidating the advantages and drawbacks of RAILE is still lacking. In this article, we will review the surgical techniques, both short and long-term outcomes, the learning curve, and explicate the current progress and clinical efficacy of RAILE.

Considerations for the Surgical Management of Thoracic Cancers During the COVID-19 Pandemic: Rational Strategies for Thoracic Surgeons.

Objective: The novel Coronavirus Disease 2019 (COVID-19) has resulted in a global health crisis since first case was identified in December 2019. As the pandemic continues to strain global public health systems, elective surgeries for thoracic cancer, such as early-stage lung cancer and esophageal cancer (EC), have been postponed due to a shortage of medical resources and the risk of nosocomial transmission. This review is aimed to discuss the influence of COVID-19 on thoracic surgical practice, prevention of nosocomial transmission during the pandemic, and propose modifications to the standard practices in the surgical management of different thoracic cancer. Methods: A literature search of PubMed, Medline, and Google Scholar was performed for articles focusing on COVID-19, early-stage lung cancer, and EC prior to 1 July 2021. The evidence from articles was combined with our data and experience. Results: We review the challenges in the management of different thoracic cancer from the perspectives of thoracic surgeons and propose rational strategies for the diagnosis and treatment of early-stage lung cancer and EC during the COVID-19 pandemic. Conclusions: During the COVID-19 pandemic, the optimization of hospital systems and medical resources is to fight against COVID-19. Indolent early lung cancers, such as pure ground-glass nodules/opacities (GGOs), can be postponed with a lower risk of progression, while selective surgeries of more biologically aggressive tumors should be prioritized. As for EC, we recommend immediate or prioritized surgeries for patients with stage Ib or more advanced stage and patients after neoadjuvant therapy. Routine COVID-19 screening should be performed preoperatively before thoracic surgeries. Prevention of nosocomial transmission by providing appropriate personal protective equipment (PPE), such as N-95 respirator masks with eye protection to healthcare workers, is necessary.

Cuprous oxide-based nanocrystals with combined chemo/chemodynamic therapy to increase tumor drug sensitivity by reducing mitochondria-derived adenosine-triphosphate.

Gastrointestinal (GI) tumor is a serious disease with high mortality rates and morbidity rates worldwide. Chemotherapy is a key treatment for GI, however, systematic side effects and inevitable drug resistance complicate the situation. In the process of therapy, P-glycoprotein (P-gp) could remove chemotherapy drugs from cells, thus causing multi-drug resistance. Chemodynamic therapy (CDT) utilizing Fenton chemistry has been used for cancer therapy, along with various combination therapies. The reactive oxygen species produced by CDT could inhibit P-gp's efflux pump function, which reduce chemoagents excretion and reverse drug resistance. In the present study, we developed novel nanocrystals (Cu2O@Pt NCs) to overcome drug resistance by reducing mitochondria-derived ATP through chemo/CDT in GI cancer. Furthermore, in vivo results in tumor-bearing mice demonstrated that treatment with Cu2O@Pt NCs with CDT and chemotherapy could achieve the most effective antitumor therapeutic effect with the least amounts of adverse effects. As a result, Cu2O@Pt NCs could provide a promising strategy for chemo/CDT-synergistic therapy.

Physicochemical properties and immune-enhancing activity of graded polysaccharides from the peels of stem lettuce (Lactuca sativa) by cascade membrane technology.

In this study, cascade membrane technology was applied to classify polysaccharides from the peels of stem lettuce (PPSLs), and three graded polysaccharides (PPSL100, PPSL10, and PPSL1) were obtained using ultrafiltration membranes of 100, 10, and 1 kDa in sequence. The physicochemical properties and immune-modulatory activity of three PPSLs fractions were analyzed and compared. Results showed that all three fractions have characteristic absorption peak of polysaccharides determined by FT-IR, and their monosaccharide composition only consisted of glucose determined by HPLC. PPSL10 had the highest contents of total sugar (88.09 ± 3.52%), uronic acid (2.55 ± 0.10%), and sulfate group (4.15 ± 0.20%). Besides, all three fractions exhibited immune-enhancing activities using RAW264.7 macrophages model, and PPSL10 was the best able to promote phagocytosis of neutral red and nitric oxide generation, which might relate to the high contents of above compositions and medium molecular weight (32 kDa). The findings indicated that PPSL10 could be developed as immune-modulator in the field of functional foods.