Tumor Microenvironment Modulation by Neoadjuvant Erlotinib Therapy and Its Clinical Impact on Operable EGFR-Mutant Non-Small Cell Lung Cancer.

PURPOSE: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors have greatly improved survival in EGFR-mutant (EGFRm) non-small cell lung cancer (NSCLC); however, their effects on the tumor microenvironment (TME) are unknown. We assessed the changes induced by neoadjuvant erlotinib therapy (NE) in the TME of operable EGFRm NSCLC. MATERIALS AND METHODS: This was a single-arm phase II trial for neoadjuvant/adjuvant erlotinib therapy in patients with stage II/IIIA EGFRm NSCLC (EGFR exon 19 deletion or L858R mutations). Patients received up to 2 cycles of NE (150 mg/day) for 4 weeks, followed by surgery and adjuvant erlotinib or vinorelbine plus cisplatin therapy depending on observed NE response. TME changes were assessed based on gene expression analysis and mutation profiling. RESULTS: A total of 26 patients were enrolled; the median age was 61, 69% were female, 88% were stage IIIA, and 62% had L858R mutation. Among 25 patients who received NE, the objective response rate was 72% (95% confidence interval [CI], 52.4 to 85.7). The median disease-free and overall survival (OS) were 17.9 (95% CI, 10.5 to 25.4) and 84.7 months (95% CI, 49.7 to 119.8), respectively. Gene set enrichment analysis in resected tissues revealed upregulation of interleukin, complement, cytokine, transforming growth factor ß, and hedgehog pathways. Patients with upregulated pathogen defense, interleukins, and T-cell function pathways at baseline exhibited partial response to NE and longer OS. Patients with upregulated cell cycle pathways at baseline exhibited stable/progressive disease after NE and shorter OS. CONCLUSION: NE modulated the TME in EGFRm NSCLC. Upregulation of immune-related pathways was associated with better outcomes.

Treatment Outcomes of Proton Beam Therapy for Esophageal Squamous Cell Carcinoma at a Single Institute.

Recently, proton beam therapy (PBT) has gathered attention for improving outcomes and reducing toxicities in various cancers; however, the evidence for esophageal squamous cell carcinoma (ESCC) is lacking. Our study retrospectively evaluated the outcomes of PBT for ESCC patients at a single institute. The patients treated with PBT between November 2015 and February 2022 were included in the study, excluding those with distant metastases or those that had undertaken prior treatment for esophageal cancer (EC). The 3 year overall survival (OS) and progression-free survival (PFS) rates were calculated based on stage grouping. The patterns of failure, salvage treatment outcomes, and toxicity profiles were analyzed. The median follow-up was 35.1 months, and 132 patients were analyzed. The 3 year OS and PFS rates for the stages I, II, and III disease cases were 81.0%, 62.9%, and 51.3%; and 70.6%, 71.8%, and 39.8%, respectively. Nineteen patients presented isolated local progression, ten patients underwent appropriate salvage procedures, and nine were successfully salvaged. One patient with isolated regional progression was also salvaged. No cases of grade ≥ 4 lymphopenia were observed. One patient had grade 4 pericardial effusion and esophageal fistula. For the patients with ESCC, PBT is an effective treatment in terms of the survival outcomes and toxicities.

Rapid and Sensitive Detection of Antibiotic Resistance Genes by Utilizing TALEs as a Diagnostic Probe with 2D-Nanosheet Graphene Oxide.

As antibiotic resistance has risen as one of the major health concerns associated with infectious diseases due to the reduced efficacy of antibiotics, rapid and sensitive detection of antibiotic resistance genes is critical for more effective and faster treatment of infectious diseases. A class of programmable DNA-binding domains called transcriptional activator-like effectors (TALEs) provides a novel scaffold for designing versatile DNA-binding proteins due to their modularity and predictability. Here, we developed a simple, rapid, and sensitive system for detecting antibiotic resistance genes by exploring the potential of TALE proteins for the creation of a sequence-specific DNA diagnostic along with 2D-nanosheet graphene oxide (GO). TALEs were engineered to directly recognize the specific double-stranded (ds) DNA sequences present in the tetracycline resistance gene (tetM), avoiding the need for dsDNA denaturation and renaturation. We take advantage of the GO as an effective signal quencher to quantum dot (QD)-labeled TALEs for creating a turn-on strategy. QD-labeled TALEs are adsorbed on the GO surface, which will bring QDs in close proximity to GO. Due to the fluorescence quenching ability of GO, QDs are expected to be quenched by GO via fluorescence resonance energy transfer (FRET). QD-labeled TALE binding to the target dsDNA would lead to the conformational change, which would result in dissociation from the GO surface, thereby restoring the fluorescence signal. Our sensing system was able to detect low concentrations of dsDNA sequences in the tetM gene after only 10-minute incubation with the DNA, providing a limit of detection as low as 1 fM of Staphylococcus aureus genomic DNA. This study demonstrated that our approach of utilizing TALEs as a new diagnostic probe along with GO as a sensing platform can provide a highly sensitive and rapid method for direct detection of the antibiotic resistance gene without requiring DNA amplification or labeling.

Prediction Models for Mediastinal Metastasis and Its Detection by Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration in Potentially Operable Non-Small Cell Lung Cancer: A Prospective Study.

BACKGROUND: Prediction models for mediastinal metastasis and its detection by endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) have not been developed using a prospective cohort of potentially operable patients with non-small cell lung cancer (NSCLC). RESEARCH QUESTION: Can mediastinal metastasis and its detection by EBUS-TBNA be predicted with prediction models in NSCLC? STUDY DESIGN AND METHODS: For the prospective development cohort, 589 potentially operable patients with NSCLC were evaluated (July 2016-June 2019) from five Korean teaching hospitals. Mediastinal staging was performed using EBUS-TBNA (with or without the transesophageal approach). Surgery was performed for patients without clinical N (cN) 2-3 disease by endoscopic staging. The prediction model for lung cancer staging-mediastinal metastasis (PLUS-M) and a model for mediastinal metastasis detection by EBUS-TBNA (PLUS-E) were developed using multivariable logistic regression analyses. Validation was performed using a retrospective cohort (n = 309) from a different period (June 2019-August 2021). RESULTS: The prevalence of mediastinal metastasis diagnosed by EBUS-TBNA or surgery and the sensitivity of EBUS-TBNA in the development cohort were 35.3% and 87.0%, respectively. In PLUS-M, younger age (< 60 years and 60-70 years compared with ≥ 70 years), nonsquamous histology (adenocarcinoma and others), central tumor location, tumor size (> 3-5 cm), cN1 or cN2-3 stage by CT, and cN1 or cN2-3 stage by PET-CT were significant risk factors for N2-3 disease. Areas under the receiver operating characteristic curve (AUCs) for PLUS-M and PLUS-E were 0.876 (95% CI, 0.845-0.906) and 0.889 (95% CI, 0.859-0.918), respectively. Model fit was good (PLUS-M: Hosmer-Lemeshow P = .658, Brier score = 0.129; PLUS-E: Hosmer-Lemeshow P = .569, Brier score = 0.118). In the validation cohort, PLUS-M (AUC, 0.859 [95% CI, 0.817-0.902], Hosmer-Lemeshow P = .609, Brier score = 0.144) and PLUS-E (AUC, 0.900 [95% CI, 0.865-0.936], Hosmer-Lemeshow P = .361, Brier score = 0.112) showed good discrimination ability and calibration. INTERPRETATION: PLUS-M and PLUS-E can be used effectively for decision-making for invasive mediastinal staging in NSCLC. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT02991924; URL: www. CLINICALTRIALS: gov.

Association between N-Terminal Prohormone Brain Natriuretic Peptide and Decreased Skeletal Muscle Mass in a Healthy Adult Population: A Cross-Sectional Study.

BACKGRUOUND: Although an inverse association between the N-terminal prohormone brain natriuretic peptide (NT-proBNP) and obesity exists, only few major studies have assessed the association between NT-proBNP levels and skeletal muscle mass in asymptomatic healthy adults. Therefore, this cross-sectional study was conducted. METHODS: We assessed participants who underwent health examinations at Kangbuk Samsung Hospital in South Korea from January 2012 to December 2019. Appendicular skeletal muscle mass was measured using a bioelectrical impedance analyzer, and the skeletal muscle mass index (SMI) was calculated. Participants were divided into the control, mildly low skeletal muscle mass (LMM) (-2 standard deviation [SD] < SMI ≤-1 [SD]), and severely LMM groups (SD ≤-2) based on their SMI. The association between elevated NT-proBNP level (≥125 pg/mL) and skeletal muscle mass was assessed using multivariable logistic regression analysis with adjustment for confounding factors. RESULTS: This study enrolled 15,013 participants (mean age, 37.52±9.52; men, 54.24%; control, n=12,827; mildly LMM, n=1,998; severely LMM, n=188). Prevalence of elevated NT-proBNP was higher in mildly and severely LMM groups than in the control group (control, 1.19%; mildly LMM, 1.4%; severely LMM, 4.26%; P=0.001). The adjusted odds ratio (OR) of elevated NT-proBNP was significantly higher in severely LMM (OR, 2.87; 95% confidence interval [CI], 1.3 to 6.37) than in control (OR, 1.00; reference) or mildly LMM groups (OR, 1.24; 95% CI, 0.81 to 1.89). CONCLUSION: Our results showed that NT-proBNP elevation were more prevalent in participants with LMM. In addition, our study showed an association between skeletal muscle mass and NT-proBNP level in a relatively young and healthy adult population.

Immune Responses to Plant-Derived Recombinant Colorectal Cancer Glycoprotein EpCAM-FcK Fusion Protein in Mice.

Epidermal cell adhesion molecule (EpCAM) is a tumor-associated antigen (TAA), which has been considered as a cancer vaccine candidate. The EpCAM protein fused to the fragment crystallizable region of immunoglobulin G (IgG) tagged with KDEL endoplasmic reticulum (ER) retention signal (EpCAM-FcK) has been successfully expressed in transgenic tobacco (Nicotiana tabacum cv. Xanthi) and purified from the plant leaf. In this study, we investigated the ability of the plant-derived EpCAM-FcK (EpCAM-FcKP) to elicit an immune response in vivo. The animal group injected with the EpCAM-FcKP showed a higher differentiated germinal center (GC) B cell population (~9%) compared with the animal group injected with the recombinant rhEpCAM-Fc chimera (EpCAM-FcM). The animal group injected with EpCAM-FcKP (~42%) had more differentiated T follicular helper cells (Tfh) than the animal group injected with EpCAM-FcM (~7%). This study demonstrated that the plant-derived EpCAM-FcK fusion antigenic protein induced a humoral immune response in mice.

A Comparative Analysis of Photon versus Proton Beam Therapy in Neoadjuvant Concurrent Chemoradiotherapy for Intrathoracic Squamous Cell Carcinoma of the Esophagus at a Single Institute.

BACKGROUND: Proton beam therapy (PBT), as a neoadjuvant chemoradiotherapy (nCRT) modality, is expected to result in better outcomes than photon-based radiotherapy (RT) for esophageal cancer, particularly adenocarcinoma. This study reports the results of nCRT for locally advanced esophageal squamous cell carcinoma (ESCC) using both modalities. METHODS: We retrospectively reviewed the records of patients who underwent nCRT for ESCC between 2001 and 2020. A median of 41.4 Gy or cobalt gray equivalents of radiation was delivered using either photons or protons, with concurrent chemotherapy. Dosimetric and clinical parameters were compared between the two groups. RESULTS: Of the 31 patients, the lungs and heart of the proton group (n = 15) were exposed to significantly less radiation compared to the photon group (n = 16). No significant differences in short-term postoperative outcomes or lymphocyte count were observed between the groups, and there were no significant differences between the photon and proton groups in 2-year overall survival (67.8% vs. 68.6%, p = 0.867) or 2-year disease-free survival (33.3% vs. 34.5%, p = 0.749), with a median follow-up of 17 months. CONCLUSIONS: PBT provided a significant dosimetric benefit over photon-based RT during nCRT for ESCC; however, it did not improve clinical outcomes.

Evaluation of a Smart After-Care Program for Patients with Lung Cancer: A Prospective, Single-Arm Pilot Study.

BACKGROUND: The efficacy of telemedicine among cancer survivors is uncertain. The Smart After-Care Program (SAP), which is an interactive, smartphone-based remote health monitoring system, was developed to help patients manage their health after leaving the hospital. This study was designed to evaluate the efficacy of our remote health care program for lung cancer patients. METHODS: We enrolled 50 patients with lung cancer. Self-monitoring devices were supplied to all patients, who were instructed to enter their daily vital signs and subjective symptoms to the Smart After-Care app. The app also provided information about rehabilitation exercises and a healthy diet for lung cancer patients. All patients received health counseling via telephone once a week and visited an outpatient clinic during weeks 6 and 12 to assess satisfaction with the SAP and changes in quality of life and physical performance. RESULTS: Overall satisfaction with the SAP was very high (very good, 61.9%; good, 26.2%). In the multivariate analysis to identify factors affecting satisfaction, the distance between the patient's residence and the hospital was the only significant independent factor (p=0.013). Quality of life improved along all functional scales (p<0.05). Muscle strength significantly improved in the lower limbs (p=0.012). Two-minute walk distance also significantly improved (p=0.028). CONCLUSION: This study demonstrated that the SAP was acceptable for and supportive of patients with reduced pulmonary function after lung cancer treatment. The SAP was found to be particularly useful for patients living far from the hospital.

Transabdominal cardiophrenic lymph node dissection for cytoreductive surgery in advanced ovarian cancer.

OBJECTIVE: Minimizing residual tumors is one of the most important prognostic factors in the management of advanced ovarian cancer [1]. In ovarian cancer patients with cardiophrenic lymph node (LN) metastases, transabdominal cardiophrenic lymph node dissection (CPLND) has been performed along with the surgery on the primary site [2]. However, CPLND for the complicated locations in the thoracic cavity is still technically challenging. This video aims to share our surgical technique for the transabdominal CPLND. METHODS: A 60-year-old woman who presented with suspicious bilateral ovarian cancer was hospitalized for cytoreductive surgery. Preoperative CT demonstrated peritoneal seeding and multiple LN metastases including right anterior, lateral, posterior, and left anterior cardiophrenic LNs. The gynecology and general surgery team underwent hysterectomy, bilateral salpingo-oophorectomy, supracolic omentectomy, lower anterior resection, right diaphragmatic and bladder peritonectomy, pelvic and paraaortic LN dissection, and appendectomy. The thoracic surgeon took over the operation because the pelvic cavity was regarded as R0. CPLND was performed by transabdominal, subxiphoid approach. The procedure is narrated in the video. RESULTS: Complete clearance of CPLN leaving no gross residual disease was possible without complication. A long, transverse incision of the anterior diaphragm was closed with a 1-0 polypropylene in the way of double layered continuous running suture and 8 times ties for the final knot. CONCLUSION: Transabdominal CPLND can be used safely and effectively without change of patient's position and with minimal diaphragmatic injury. However, this approach may be unfeasible for metastatic internal mammary LN dissection and still needs meticulous surgical skills to avoid complications.

Long-term Survival According to N Stage Diagnosed by Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration in Non-small Cell Lung Cancer.

BACKGROUND: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is the main procedure for mediastinal staging. However, long-term survival analyses according to clinical nodal stage diagnosed by EBUS-TBNA (eN stage) have not been reported. The value of EBUS-TBNA has not been assessed through an analysis of survival in false-negative EBUS-TBNA cases. RESEARCH QUESTION: What is the prognostic impact of eN stage in non-small cell lung cancer (NSCLC)? What is the survival rate in false-negative EBUS-TBNA cases? STUDY DESIGN AND METHODS: We retrospectively (January 2006 to December 2011) reviewed the medical records of patients with NSCLC who underwent EBUS-TBNA (± transesophageal approach) for initial staging (N = 1,089). Mediastinoscopy was not performed for EBUS-TBNA-negative cases. We performed 5-year survival analyses according to eN stage and treatment modality. Survival in false-negative EBUS-TBNA cases was compared with that in patients with pN0-1, including 941 non-EBUS-TBNA cases, during the same period. RESULTS: Among the 1,089 patients undergoing EBUS-TBNA (eN0-1: n = 681; eN2: n = 314; eN3: n = 94), we observed significant differences in survival between the eN stages (eN0-1 vs eN2: P < .0001; eN2 vs eN3: P = .0118; estimated 5-year overall survival [5YOS] rate: eN0-1 = 57.4%, eN2 = 23.2%, eN3 = 12.8%). Surgery cases had better survival than nonsurgery cases among patients with eN0-1 and eN2 (eN0-1/surgery vs eN0-1/no surgery: P < .0001; eN2/surgery vs eN2/no surgery: P < .0001). Among the patients with eN0-1, there were 55 false-negative cases (eN0-1/pN2-3, pN2: n = 54; pN3: n = 1). The 5YOS rates of patients with pN0, pN1, and eN0-1/pN2-3 were 76.4%, 56.0%, and 56.4%, respectively. Patients with eN0-1/pN2-3 had worse survival than patients with pN0 (P = .0061), whereas there was no significant difference compared with patients with pN1 (P = .9191). INTERPRETATION: Long-term survival significantly differed according to eN stage in NSCLC, highlighting the importance of EBUS-TBNA in NSCLC staging. False-negative EBUS-TBNA cases had favorable survival which was similar to that of patients with pN1, which may provide a rationale for performing surgery after negative EBUS-TBNA results.

Effect of an Endoplasmic Reticulum Retention Signal Tagged to Human Anti-Rabies mAb SO57 on Its Expression in Arabidopsis and Plant Growth.

Transgenic Arabidopsis thaliana expressing an anti-rabies monoclonal antibody (mAb), SO57, was obtained using Agrobacterium-mediated floral dip transformation. The endoplasmic reticulum (ER) retention signal Lys-Asp-Glu-Leu (KDEL) was tagged to the C-terminus of the anti-rabies mAb heavy chain to localize the mAb to the ER and enhance its accumulation. When the inaccurately folded proteins accumulated in the ER exceed its storage capacity, it results in stress that can affect plant development and growth. We generated T1 transformants and obtained homozygous T3 seeds from transgenic Arabidopsis to investigate the effect of KDEL on plant growth. The germination rate did not significantly differ between plants expressing mAb SO57 without KDEL (SO plant) and mAb SO57 with KDEL (SOK plant). The primary roots of SOK agar media grown plants were slightly shorter than those of SO plants. Transcriptomic analysis showed that expression of all 11 ER stress-related genes were not significantly changed in SOK plants relative to SO plants. SOK plants showed approximately three-fold higher mAb expression levels than those of SO plants. Consequently, the purified mAb amount per unit of SOK plant biomass was approximately three times higher than that of SO plants. A neutralization assay revealed that both plants exhibited efficient rapid fluorescent focus inhibition test values against the rabies virus relative to commercially available human rabies immunoglobulins. KDEL did not upregulate ER stress-related genes; therefore, the enhanced production of the mAb did not affect plant growth. Thus, KDEL fusion is recommended for enhancing mAb production in plant systems.

Application of Engineered Zinc Finger Proteins Immobilized on Paramagnetic Beads for Multiplexed Detection of Pathogenic DNA.

Micro-scale magnetic beads are widely used for isolation of proteins, DNA, and cells, leading to the development of in vitro diagnostics. Efficient isolation of target biomolecules is one of the keys to developing a simple and rapid point-of-care diagnostic. A zinc finger protein (ZFP) is a double-stranded (ds) DNA-binding domain, providing a useful scaffold for direct reading of the sequence information. Here, we utilized two engineered ZFPs (Stx2-268 and SEB-435) to detect the Shiga toxin (stx2) gene and the staphylococcal enterotoxin B (seb) gene present in foodborne pathogens, Escherichia coli O157 and Staphylococcus aureus, respectively. Engineered ZFPs are immobilized on a paramagnetic bead as a detection platform to efficiently isolate the target dsDNA-ZFP bound complex. The small paramagnetic beads provide a high surface area to volume ratio, allowing more ZFPs to be immobilized on the beads, which leads to increased target DNA detection. The fluorescence signal was measured upon ZFP binding to fluorophore-labeled target dsDNA. In this study, our system provided a detection limit of ≤ 60 fmol and demonstrated high specificity with multiplexing capability, suggesting a potential for development into a simple and reliable diagnostic for detecting multiple pathogens without target amplification.

Photon Versus Proton Beam Therapy for T1-3 Squamous Cell Carcinoma of the Thoracic Esophagus Without Lymph Node Metastasis.

BACKGROUND AND PURPOSE: We compared treatment outcomes and toxicities of photon radiotherapy versus proton beam therapy (PBT) and evaluated radiation field effects for T1-3 squamous cell carcinoma of the thoracic esophagus (EC) without lymph node metastasis. METHODS: Medical records of 77 patients with T1-3N0M0 thoracic EC treated with radiotherapy between 2011 and 2019 were retrospectively analyzed. Among these patients, 61 (79.2%) individuals had T1 EC. The initial clinical target volume encompassed the whole esophagus with or without supraclavicular and/or abdominal lymph nodes (extended-field radiotherapy; 67 patients, 87.0%) or the area 3-5 cm craniocaudally and 1-2 cm radially from the gross tumor volume (involved-field radiotherapy; 10 patients, 13.0%). The final clinical target volume included margins of at least 1 cm from the gross tumor volume, with total radiation doses of 50-66 (median, 66) cobalt gray equivalent. Three-dimensional conformal radiotherapy, intensity-modulated radiotherapy, and PBT were used in twenty-four, five, and forty-eight patients, respectively. Concurrent chemotherapy was administered to 17 (22.0%) patients overall and only five (8.0%) T1 patients. RESULTS: PBT showed significantly lower lung and heart radiation exposure in mean dose, V5, V10, V20, and V30 than photon radiotherapy. The median follow-up for all patients was 46 (interquartile range, 22-72) months. The 5-year progression-free survival and overall survival rates were 56.5 and 64.9%, respectively, with no significant survival difference between photon radiotherapy and PBT. In patients with T1 EC, 5-year progression-free survival and overall survival rates were 62.6 and 73.5%, respectively. CONCLUSIONS: Extended-field radiotherapy using modern radiotherapy techniques without chemotherapy showed satisfactory clinical outcomes for lymph node-negative T1 EC.

Graphene Oxide-Based Simple and Rapid Detection of Antibiotic Resistance Gene via Quantum Dot-Labeled Zinc Finger Proteins.

With the increasing rise of antibiotic-resistant pathogens, a simple and rapid detection of antibiotic resistance gene (ARG) is crucial to mitigate the spreading of antibiotic resistance. DNA-binding zinc finger proteins (ZFPs) can be engineered to recognize specific double-stranded (ds) DNA sequences in ARG. Here, we designed a simple and rapid method to detect ARG in bacteria utilizing engineered ZFPs and 2D nanosheet graphene oxide (GO) as a sensing platform. Our approach relies on the on and off effect of fluorescence signal in the presence and absence of target ARG, respectively. By taking advantage of the unique quenching capability of GO due to its electronic property, quantum dot (QD)-labeled ZFPs are adsorbed onto the GO sheets, and their fluorescence signal is quenched by proximal GO sheets through fluorescence resonance energy transfer (FRET). In the presence of target DNA, ZFP binding to the target DNA induces dissociation from GO, thereby restoring the fluorescence signal. Our system detects target DNA through restoration of QD emission as the restored signal increases directly with target DNA concentrations. Engineered ZFPs were able to detect specific dsDNA of the tetracycline resistance gene tetM with high specificity after only 10 min incubation on our GO-based sensing system. Our sensing system employed one-step FRET-based ZFP and GO combined technology to enable rapid and quantitative detection of ARG, providing a limit of detection as low as 1 nM. This study demonstrated the application of GO in conjunction with engineered DNA-binding domains for the direct detection of dsDNA with great potential as a rapid and reliable screening and detecton method against the growing threat of antibiotic resistant bacteria.

Size and extranodal extension of metastatic lymph nodes in lung adenocarcinoma.

BACKGROUND: This study assessed the prognostic significance of metastatic lymph node size (MLNS) and extranodal extension (EN) in patients with node-positive lung adenocarcinoma (ADC). METHODS: Prognostic factors influencing survival were analyzed, including age, sex, extent of operation, T- and N-stage, size of tumor, postoperative chemotherapy, presence of EN, and MLNS (>7.0 vs. ≤7.0 mm). RESULTS: Three hundred seventy-five patients met the inclusion criteria were enrolled (mean age: 59.8±10.5 years). Increasing MLNS was significantly correlated with large tumor size (P=0.015), advanced N status (P<0.001), and presence of EN (P<0.001). In multivariable analysis, large tumor size [hazard ratio (HR) 1.135, 95% confidence interval (CI): 1.050 to 1.228, P<0.001], adjuvant chemotherapy (HR 0.582, 95% CI: 0.430 to 0.787, P<0.001), EN (HR 1.454, 95% CI: 1.029 to 2.055, P=0.034), and MLNS greater than 7 mm (HR 1.741, 95% CI: 1.238 to 2.447, P<0.001) were significant prognostic factors for survival. Patients were classified into 3 groups: Group A, MLNS ≤7.0 mm/EN (-); Group B, MLNS ≤7.0 mm/EN (+) or MLNS >7.0 mm/EN (-); and Group C, MLNS >7.0 mm/EN (+). The 5-year overall survival (OS) was 72.2%, 59.0%, and 38.5% in Groups A, B and C, respectively (P<0.001). CONCLUSIONS: The MLNS and presence of EN could provide an important prognostic implication for patients with node-positive lung ADC.

Delayed Gastric Emptying after Esophagectomy: Management and Prevention.

The quality of life associated with eating is becoming an increasingly significant problem for patients who undergo esophagectomy as a result of the improved survival rate after esophageal cancer surgery. Delayed gastric emptying (DGE) is a common complication after esophagectomy. Although several strategies have been proposed for the management and prevention of DGE, no clear consensus exists. The purpose of this review is to present a brief overview of DGE and to help clinicians choose the most appropriate treatment through an analysis of DGE by cause. Furthermore, we would like to suggest some tips to prevent DGE based on our experience.

The major effects of health-related quality of life on 5-year survival prediction among lung cancer survivors: applications of machine learning.

The primary goal of this study was to evaluate the major roles of health-related quality of life (HRQOL) in a 5-year lung cancer survival prediction model using machine learning techniques (MLTs). The predictive performances of the models were compared with data from 809 survivors who underwent lung cancer surgery. Each of the modeling technique was applied to two feature sets: feature set 1 included clinical and sociodemographic variables, and feature set 2 added HRQOL factors to the variables from feature set 1. One of each developed prediction model was trained with the decision tree (DT), logistic regression (LR), bagging, random forest (RF), and adaptive boosting (AdaBoost) methods, and then, the best algorithm for modeling was determined. The models' performances were compared using fivefold cross-validation. For feature set 1, there were no significant differences in model accuracies (ranging from 0.647 to 0.713). Among the models in feature set 2, the AdaBoost and RF models outperformed the other prognostic models [area under the curve (AUC) = 0.850, 0.898, 0.981, 0.966, and 0.949 for the DT, LR, bagging, RF and AdaBoost models, respectively] in the test set. Overall, 5-year disease-free lung cancer survival prediction models with MLTs that included HRQOL as well as clinical variables improved predictive performance.

A Regulatory Noncoding RNA, nc886, Suppresses Esophageal Cancer by Inhibiting the AKT Pathway and Cell Cycle Progression.

nc886 is a regulatory non-coding RNA (ncRNA) whose expression is frequently silenced in malignancies. In the case of esophageal squamous cell carcinoma (ESCC), nc886 silencing is associated with shorter survival of patients, suggesting nc886's tumor suppressor role in ESCC. However, this observation has not been complemented by an in-detail study about nc886's impact on gene expression and cellular phenotypes. Here we have shown that nc886 inhibits AKT, a key protein in a renowned pro-survival pathway in cancer. nc886-silenced cells (nc886- cells) have activated AKT and altered expression of cell cycle genes. nc886- cells tend to have lower expression of CDKN2A and CDKN2C, both of which are inhibitors for cyclin-dependent kinase (CDK), and higher expression of CDK4 than nc886-expressing cells. As a result, nc886- cells are hyperactive in the progression of the G1 to S cell cycle phase, proliferate faster, and are more sensitive to palbociclib, which is a cancer therapeutic drug that targets CDK4/6. Experimentally by nc886 expression and knockdown, we have determined the AKT target genes and cell cycle genes that are controlled by nc886 (nc886-associated gene sets). These gene sets, in combination with pathologic staging and nc886 expression levels, are a vastly superior predictor for the survival of 108 ESCC patients. In summary, our study has elucidated in ESCC how nc886 inhibits cell proliferation to explain its tumor suppressor role and identified gene sets that are of future clinical utility, by predicting patient survival and responsiveness to a therapeutic drug.

Efficacy of health coaching and a web-based program on physical activity, weight, and distress management among cancer survivors: A multi-centered randomised controlled trial.

OBJECTIVES: To investigate the efficacy of health coaching and a web-based program on survivor physical activity (PA), weight, and distress management among stomach, colon, lung and breast cancer patients. METHODS: This randomised, controlled, 1-year trial conducted in five hospitals recruited cancer survivors within 2 months of completing primary cancer treatment who had not met ≥1 of these behavioural goals: (i) conducting moderate PA for at least 150 minutes/week or strenuous exercise for over 75 minutes per week or, in the case of lung cancer patients, low or moderate intensity exercise for over 12.5 MET per week, (ii) maintaining normal weight, and (iii) attaining a score >72 in the Post Traumatic Growth Inventory (PTGI). Participants were randomly assigned to one of three groups: the control group, a web-only group, or a health coaching + web group. The primary endpoint was based on a composite of PA, weight, and PTGI score at 12 months. RESULTS: Patients in the health coaching + web group (difference = 6.6%, P = .010) and the web-only group (difference = 5.9%, P = .031) had greater overall improvements across the three-outcome composite than the control group. The health coaching + web group had greater overall improvement in PTGI (difference = 12.6%; P < .001) than the control group, but not in PA and weight. CONCLUSION: The web-based program, with or without health coaching, may improve health behaviours including PA, weight, and distress management among cancer survivors within 2 months of completing primary cancer treatment. The web-based program with health coaching was mainly effective for reducing psychological distress.

The association of physical function and quality of life on physical activity for non-small cell lung cancer survivors.

PURPOSE: Our study aimed to assess the association between physical function and quality of life (QOL) with physical activity among non-small cell lung cancer (NSCLC) survivors. METHODS: Participants were 92 NSCLC survivors. Physical activity was assessed by a self-report with physiatrist's interview and the Korean version of the short form of the International Physical Activity Questionnaire (IPAQ-SF). All participants were required to perform three standardized fitness tests. The Korean version of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) was used to assess QOL. Factors associated with physical functioning and QOL were determined using multiple linear regression. RESULTS: A significant correlation between metabolic equivalent task minutes per week (MET-min/wk) and aerobic fitness was found (r = 0.277, p = 0.008). Factors associated with aerobic fitness include gender, age, and MET-min/wk. The meeting physical activity guideline group was also a factor associated with aerobic fitness. In the QOL aspect, a significant correlation between MET-min/wk and some QOL score was found. The meeting physical activity guideline group was a factor associated with QOL (global health status, physical function, and role function), not total MET-min/wk. CONCLUSIONS: Increased physical activity was associated with higher aerobic fitness and QOL. Engagement in physical activity that met physical activity guidelines was a factor related to aerobic fitness and better QOL in some domains. To improve aspects of aerobic fitness and QOL, we may consider the pattern of physical activity, including regular participation and intensity, rather than total physical activity including basal activity.