Tele-Assisted Home-Based Palliative Care Reduces Health Care Costs for Terminal Cancer Patients: Real-World Evidence From a Regional Hospital in Taiwan.

Background: Tele-assisted home-based palliative care (THPC) usually fulfills the desire of terminal patients to pass away at home. The overall costs of such a service deserve evaluation. Objectives: This study aims to determine health care utilization and costs for cancer patients at the end of life, stratified by THPC service. Design: Patients who received THPC were matched 1:1 based on age, gender, year of death, and propensity score with those who did not receive THPC. Setting/Subjects: A total of 773 cancer patients passed away in a regional hospital in Taiwan during the period of 2012-2020, of which 293 received THPC. Measurements: We measured the rates and costs of outpatient clinic visits, emergency department (ED) visits, hospitalizations, and intensive care unit (ICU) admissions during the last week, the last two weeks and the last month before death. In addition, we estimated the driving times and expenses required for transportation from each cancer patient's home to the hospital using Google Maps. National Health Insurance (NHI) reimbursements and out-of-pocket expenses were also calculated. Results: In comparison with patients without THPC, those who received THPC had a 50% lower likelihood of visiting the ED or being hospitalized, a more than 90% reduced chance of ICU admission, but were four times more likely to obtain their medicines from outpatient clinics. THPC patients had similar out-of-pocket expenditures, approximately half of the NHI costs, and lower rates and costs for ambulance transportation to the ED. Conclusions: THPC reduced health care costs for terminal cancer patients in the last week, the last two weeks, and the last month before death, while also increasing the likelihood of patients being able to rest and pass away at home.

Antioxidant Mechanism, Spectroscopic and Pharmacological Properties of Four Flavonoids: DFT, Docking and Molecular Dynamics.

Myricetin (1), Quercetin (2), Kaempferol (3) and Kaempferide (4) were flavonoids with phenolic hydroxyl groups. The antioxidant and pharmacological mechanisms of them were investigated in detail. The lowest hydroxyl dissociation enthalpies of 1, 2, 3 and 4 were calculated by DFT, respectively. The hydroxyl dissociation enthalpies of the four flavonoids at the O2 site are the highest. By analyzing the intramolecular hydrogen bonds and HOMO-LUMO orbitals of the four flavonoids, the reasons for their divergence of hydroxyl dissociation enthalpies and antioxidant mechanisms were further investigated. The UV-vis and IR spectra of four flavonoids were compared. The interactions about electrostatic attraction, p-π conjugation and hydrogen bond combined the flavonoid with the target protein closely. The root mean square deviation of peroxisome proliferator-activated receptor γ combined with 1, 2 and 3 increased, while that of PPARγ combined with 4 decreased.

Estimating Taiwan's QALY league table for catastrophic illnesses: Providing real-world evidence to integrate prevention with treatment for resources allocation.

BACKGROUND/PURPOSE: Curative technologies improve patient's survival and/or quality of life but increase financial burdens. Effective prevention benefits all three. We summarize estimation methods and provide examples of how much money is spent per quality-adjusted life year (QALY) or life year (LY) on treating a catastrophic illness under a lifetime horizon and how many QALYs/LYs and lifetime medical costs (LMC) could be potentially saved by prevention. METHODS: We established cohorts by interlinkages of Taiwan's nation-wide databases including National Health Insurance. We developed methods to estimate lifetime survival functions, which were multiplied with the medical costs and/or quality of life and summed up to estimate LMC, quality-adjusted life expectancy (QALE) and lifetime average cost per QALY/LY for catastrophic illnesses. By comparing with the age-, sex-, and calendar year-matched referents simulated from vital statistics, we obtained the loss-of-QALE and loss-of-life expectancy (LE). RESULTS: The lifetime cost-effectiveness ratios of ventilator-dependent comatose patients, dialysis, spinal cord injury, major trauma, and cancers were US$ 96,800, 16,200-20,000, 5500-5,900, 3400-3,600, and 2900-11,900 per QALY or LY, respectively. The successful prevention of lung, liver, oral, esophagus, stomach, nasopharynx, or ovary cancer would potentially save US$ 28,000-97,000 and > 10 QALYs; whereas those for end-stage kidney disease, stroke, spinal injury, or major trauma would be US$ 55,000-300,000 and 10-14 QALYs. Loss-of-QALE and loss-of-LE were less confounded indicators for comparing the lifetime health benefits of different technologies estimated from real-world data. CONCLUSIONS: Integration of prevention with treatment for resources allocation seems feasible and would improve equity and efficiency.

Lymph node volume predicts survival in esophageal squamous cell carcinoma treated with neoadjuvant chemoradiotherapy and surgery.

Large primary tumor volume has been identified as a poor prognostic factor of esophageal squamous cell carcinoma (ESCC) treated with definitive concurrent chemoradiotherapy (CCRT). However, when neoadjuvant CCRT and surgery are adopted, the prognostic impact of primary tumor and lymph node (LN) volume on clinical outcomes in ESCC remains to be elucidated. This study included 107 patients who received neoadjuvant CCRT and surgery for ESCC. The volume of the primary tumor and LN was measured using radiotherapy planning computed tomography scans, and was correlated with overall survival (OS), disease-free survival (DFS), and cancer failure pattern. The median OS was 24.2 months (IQR, 11.1-93.9) after a median follow-up of 18.4 months (IQR, 8.1-40.7). The patients with a baseline LN volume > 7.7 ml had a significantly worse median OS compared to those with smaller LN volume (18.8 vs. 46.9 months, p = 0.049), as did those with tumor regression grade (TRG) 3-5 after CCRT (13.9 vs. 86.7 months, p < 0.001). However, there was no association between OS and esophageal tumor volume (p = 0.363). Multivariate analysis indicated that large LN volume (HR 1.753, 95% CI 1.015-3.029, p = 0.044) and high TRG (HR 3.276, 95% CI 1.556-6.898, p = 0.002) were negative prognostic factors for OS. Furthermore, large LN volume was linked to increased locoregional failure (p = 0.033) and decreased DFS (p = 0.041). In conclusion, this study demonstrated that large LN volume is correlated with poor OS, DFS, and locoregional control in ESCC treated with neoadjuvant CCRT and esophagectomy.

Possible overdiagnosis of early-stage lung adenocarcinoma among never-smokers in Taiwan.

10-year survival for never-smokers with >1 cm but ≤3 cm AIS/BAC/MIA was not inferior to that of the matched referents, pointing to possible overdiagnosis. Clinicians might consider adhering to Lung-RADS and watchful waiting for these non-solid nodules. https://bit.ly/41U6kxs.

Therapeutic Decision Making in Prevascular Mediastinal Tumors Using CT Radiomics and Clinical Features: Upfront Surgery or Pretreatment Needle Biopsy?

The study aimed to develop machine learning (ML) classification models for differentiating patients who needed direct surgery from patients who needed core needle biopsy among patients with prevascular mediastinal tumor (PMT). Patients with PMT who received a contrast-enhanced computed tomography (CECT) scan and initial management for PMT between January 2010 and December 2020 were included in this retrospective study. Fourteen ML algorithms were used to construct candidate classification models via the voting ensemble approach, based on preoperative clinical data and radiomic features extracted from the CECT. The classification accuracy of clinical diagnosis was 86.1%. The first ensemble learning model was built by randomly choosing seven ML models from a set of fourteen ML models and had a classification accuracy of 88.0% (95% CI = 85.8 to 90.3%). The second ensemble learning model was the combination of five ML models, including NeuralNetFastAI, NeuralNetTorch, RandomForest with Entropy, RandomForest with Gini, and XGBoost, and had a classification accuracy of 90.4% (95% CI = 87.9 to 93.0%), which significantly outperformed clinical diagnosis (p < 0.05). Due to the superior performance, the voting ensemble learning clinical-radiomic classification model may be used as a clinical decision support system to facilitate the selection of the initial management of PMT.

Losses of lifetime employment duration and productivity for patients with different subtypes and stages of lung cancer.

BACKGROUND: How different subtypes and stages of lung cancer affect morbidity- and mortality-associated productivity have not been investigated. This study quantified the losses of lifetime employment duration and productivity among patients with various subtypes and stages of lung cancer. METHODS: We identified nationwide lung cancer patients diagnosed at the ages of 50-64 between 2011 and 2019. Monthly survival probabilities were weighted by monthly employed-to-population ratios and working salaries to estimate lifetime employment duration and productivity. We compared lifetime employment duration and productivity of patients with those of the age-, sex-, calendar year-matched general population for losses of lifetime employment duration and productivity, which were multiplied by pathology and stage shifts based on the first-round screening of Taiwan Lung Cancer Screening in Never Smoker Trial (TALENT) to calculate the savings of lifetime employment duration and productivity. RESULTS: Lung cancer patients had shorter survival and employment duration than the referents. Patients with lung cancers other than adenocarcinoma experienced greater losses of lifetime employment duration and productivity as compared to adenocarcinoma patients. Applying the estimations of never-smoking patients to 100 lung cancer patients with pathology and stage shifts based on the TALENT, the savings of lifetime employment duration and productivity were 132.2 (95% prediction interval: 116.2-147.4) years and 3353 (95% prediction interval: 2914-3802) thousand US dollars, respectively. CONCLUSIONS: Early diagnosis of lung cancer would save the losses of employment duration and lifetime productivity. Future evaluation of the cost-effectiveness of lung cancer screening could consider incorporating these societal impacts.

Pulmonary-function changes after uniportal video-assisted thoracoscopic anatomical lung resection.

OBJECTIVE: The superiority of segmentectomy over lobectomy with regard to preservation of pulmonary function is controversial. This study aimed to examine changes in pulmonary function after uniportal video-assisted thoracoscopic surgery (VATS) according to the number of resected segments. METHODS: We retrospectively reviewed 135 consecutive patients who underwent anatomical lung resection via uniportal VATS from April 2015 to December 2020. Pulmonary function loss was evaluated using forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1). Patients were grouped according to number of resected segments: one-segment (n = 33), two segments (n = 22), three segments (n = 40), four segments (n = 15), and five segments (n = 25). RESULTS: Clinical characteristics did not significantly differ between groups, except for tumor size. Mean follow-up was 8.96 ± 3.16 months. FVC loss was significantly greater in five-segment resection (10.8%) than one-segment (0.97%, p = 0.008) and two-segment resections (2.44%, p = 0.040). FEV1 loss was significantly greater in five-segment resection (15.02%) than one-segment (3.83%, p < 0.001), two-segment (4.63%, p = 0.001), and three-segment resections (7.63%, p = 0.007). Mean FVC loss and FEV1 loss increased linearly from one-segment resection to five-segment resection. Mean loss in FVC and FEV1 per segment resected was 2.16% and 3.00%, respectively. CONCLUSIONS: Anatomical lung resection of fewer segments was associated with better preservation of pulmonary function in patients undergoing uniportal VATS, and function loss was approximately 2%-3% per segment resected with linear relationship.

Design, Synthesis, and Molecular Docking Study of Novel 3-Cyanopyridine Derivatives for the Anti-Cancer Drug Target Survivin Protein.

Survivin is an important member of the antiapoptotic protein family and controls the cell's life cycle. Overexpression of survivin in tumor cells leads to inhibition of apoptosis, thus contributing to cancer cell proliferation. The largest binding pocket in the survivin dimer was located in the BIR domain. The key to the efficacy of 3-cyanopyridines was their surface interaction with the survivin amino acid Ile74. METHODS: Through the optimization of the 3-cyanopyridine, 29 new compounds with a 3- Cyanopyridine structure were designed, synthesized, and characterized by NMR, IR, and mass spectrometry. The antitumor activity of the compounds in vitro was detected by the MTT method. RESULTS: In vitro anti-tumor experiments showed that some compounds exhibited good anti-cancer effects. The IC50 values of the compound 2-amino-6-(2,4-difluorophenyl)-4-(4-hydroxyphenyl) nicotinonitrile (10n) against human liver cancer (Huh7), human glioma (U251), and human melanoma (A375) cells were 5.9, 6.0 and 7.2 µM, respectively. The IC50 values of the compound 6-(2,4-difluorophenyl)- 4-(4-hydroxyphenyl)-2-oxo-1,2-dihydropyridine-3-carbonitrile (9o) against Huh7, U251 and A375 cells were 2.4, 17.5 and 7.2 µM, respectively, which were better than those of 10- hydroxycamptothecin and 5-fluorouracil. Analysis of the results of molecular dynamics simulation established that the BIR domain is the optimal binding site on the survivin protein, and the fingerprints of the eight most active compounds and the molecular docking to the survivin protein are analyzed. CONCLUSION: 3-Cyanopyridine is an excellent backbone for antitumor lead compounds, 10n and 9o, as derivatives of 3-Cyanopyridine are excellent survivin protein-targeting inhibitors worthy of further study. The key factor in inhibiting survivin protein through the action of amino acid Ile74.

Diagnostic value of apparent diffusion coefficient in predicting pathological T stage in patients with thymic epithelial tumor.

PURPOSES: This study aimed to evaluate the diagnostic capacity of apparent diffusion coefficient (ADC) in predicting pathological Masaoka and T stages in patients with thymic epithelial tumors (TETs). METHODS: Medical records of 62 patients who were diagnosed with TET and underwent diffusion-weighted imaging (DWI) prior to surgery between August 2017 and July 2021 were retrospectively analyzed. ADC values were calculated from DWI images using b values of 0, 400, and 800 s/mm2. Pathological stages were determined by histological examination of surgical specimens. Cut-off points of ADC values were calculated via receiver operating characteristic (ROC) analysis. RESULTS: Patients had a mean age of 56.3 years. Mean ADC values were negatively correlated with pathological Masaoka and T stages. Higher values of the area under the ROC curve suggested that mean ADC values more accurately predicated pathological T stages than pathological Masaoka stages. The optimal cut-off points of mean ADC were 1.62, 1.31, and 1.48 × 10-3 mm2/sec for distinguishing pathological T2-T4 from pathological T1, pathological T4 from pathological T1-T3, and pathological T3-T4 from pathological T2, respectively. CONCLUSION: ADC seems to more precisely predict pathological T stages, compared to pathological Masaoka stage. The cut-off values of ADC identified may be used to preoperatively predict pathological T stages of TETs.

Transferrin and Prealbumin Identify Esophageal Cancer Patients with Malnutrition and Poor Prognosis in Patients with Normal Albuminemia: A Cohort Study.

In this study, we aimed to analyze whether serum prealbumin and transferrin have a higher sensitivity than albumin for detecting malnutrition and predicting survival in esophageal cancer patients. A total of 212 patients were prospectively enrolled. Serum albumin, prealbumin, and transferrin were analyzed by enzyme-linked immunosorbent assays. The association of nutritional markers with survival was analyzed. We found that malnutrition was presented in 44.5% of the patients, while 56.6% were unaware of their body weight change. The area under the curve for diagnosing malnutrition was largest for prealbumin, followed by transferrin and albumin, with optimal breakpoints of 21 mg/dL, 206 mg/dL, and 4.3 g/dL, respectively, for diagnosing malnutrition. The diagnostic sensitivity for malnutrition was 34.1-63.4% with a single marker and this increased to 80.5% with all 3 markers. In patients with normal albuminemia (≥ 4.3 g/dL), a low level of prealbumin and/or transferrin predicted malnutrition and poor prognosis. Multivariate Cox regression analysis confirmed that a low level of the nutritional marker was an independent poor prognostic factor. In conclusion, serum prealbumin and transferrin outperformed albumin in identifying esophageal cancer patients with malnutrition and poor prognosis. Checking all three markers will help with the early diagnosis of malnutrition and enable timely intervention.

Carboxypeptidase E mRNA: Overexpression predicts recurrence and death in lung adenocarcinoma cancer patients.

BACKGROUND: Effective biomarkers for prediction of recurrence of lung adenocarcinoma cancer (LADC) patients are needed to determine treatment strategies post-surgery to improve outcome. OBJECTIVE: This study evaluates the efficacy of carboxypeptidase E (CPE) mRNA including its splice isoforms, CPE-ΔN, as a biomarker for predicting recurrence in adenocarcinoma patients. METHODS: RNA was extracted from resected tumors from 86 patients with different stages of non-small cell LADC. cDNA was synthesized and qRT-PCR carried out to determine the copy numbers of CPE/CPE-ΔN mRNA. Patients were followed for 7 years post-tumor resection to determine recurrence and death. RESULTS: ROC curve analysis showed the overall AUC for CPE/CPE-ΔN copy number was 0.563 in predicting recurrence and 0.562 in predicting death. Kaplan-Meier survival analysis showed statistical difference (p= 0.018), indicating that patients with high CPE/CPE-ΔN copy numbers had a shorter time of disease-free survival and also shorter time to death (p= 0.035). Subgroup analyses showed that association of disease-free survival time with CPE/CPE-ΔN copy number was stronger among stage I and II LADC patients (p= 0.047). CONCLUSIONS: CPE/CPE-ΔN mRNA is a potentially useful biomarker for predicting recurrence and death in LADC patients, especially in identifying patients at high risk of recurrence at early stages I and II.

Outcomes of salvage lung resections in advanced EGFR-mutant lung adenocarcinomas under EGFR TKIs.

BACKGROUND: Studies regarding the outcomes of salvage lung resections of epidermal growth factor receptor (EGFR)-mutant advanced lung adenocarcinomas (ALAs) following treatment with EGFR tyrosine kinase inhibitors (TKIs) are limited, hence the objective of this study was to investigate such outcomes. METHODS: A total of 29 patients with EGFR-mutant ALA who underwent salvage surgery after EGFR-TKI treatment from October 2013 through January 2019 were enrolled. The patients were divided into two groups according to the surgical indications. Their perioperative parameters and surgical outcomes, including progression-free survival (PFS) and overall survival (OS), were then analyzed. RESULTS: The initial stages of the patients were stage IIIB (seven patients), IVA (17 patients), and IVB (five patients). Their surgical indications included residual tumor (25 patients) and progressive disease (PD) (four patients). They all underwent surgery via minimally invasive approaches and the median follow-up was 33.9 months. Within that follow-up duration, the median PFS after surgery was 36.4 months, and the median OS was still not reached. There were no significant differences in PFS or OS according to the different EGFR-TKIs used, the different durations of EGFR-TKI treatment before surgery, or the different surgical indications. However, the patients presenting with pleural seeding before EGFR-TKI treatment had significantly poorer PFS and OS than the other patients (P < 0.001). CONCLUSIONS: Salvage surgery following EGFR-TKI treatment of ALAs is a safe procedure with acceptable intra- and postoperative results. However, studies involving more cases and longer follow-up periods are needed to clarify its benefits. KEY POINTS: Salvage surgery following EGFR-TKI treatment of ALAs is a safe procedure with acceptable intra- and postoperative results. Our results support the use of surgery following treatment with EGFR-TKIs such as afatinib in advanced lung cancer.

QALYs and medical costs saved from prevention of a cancer: Analysis of nation-wide real-world data of Taiwan with lifetime horizon.

BACKGROUND/PURPOSE: To quantify savings of loss-of-QALE (quality-adjusted life expectancy) and lifetime medical costs from prevention of different cancers. METHODS: We collected nation-wide data on 808,700 new cancer cases of 14 different organ systems and followed them from 1998 to 2014 in Taiwan. We also collected 13,005 cancer patients from a medical center and 47,320 repeated measurements of quality of life (QoL) of EQ-5D to obtain utility values and multiplied them with the corresponding survival rates to calculate QALE. With Kaplan-Meier estimation to survival function to the end of follow-up, we extrapolated to lifetime through a rolling over algorithm on the logit transform of the survival ratio between the index cohort and age-, sex, and calendar year matched referents simulated from vital statistics. Lifetime costs for each cancer were estimated by multiplying survival with average monthly costs after adjustment with annual discount rate. The loss-of-QALE was estimated by the difference in QALE between the index cancer cohort and corresponding referents. RESULTS: The dynamic changes and weighted averages of the QoL utility values of 14 different cancers ranged from 0.82 to 0.95. Successful prevention of liver, lung, esophagus, or nasopharynx cancer would save more than 10 quality-adjusted life years and more than 21,000 USD per case for both genders. Since the saving of loss-of-QALE was adjusted for different age, sex, and calendar-year distributions, it could be used in cost effectiveness evaluation. CONCLUSION: Savings of loss-of-QALE and lifetime costs could be used for comparison of prevention, diagnosis, treatment and rehabilitation from a lifetime horizon.

Single-port thoracoscopic anatomic resection for chronic inflammatory lung disease.

BACKGROUND: It is challenging to proceed thoracoscopic anatomic resection when encountering severe pleural adhesion or calcified peribronchial lymphadenopathy. Compared with multiple-port video-assisted thoracoscopic surgery (MP-VATS), how to overcome these challenges in single-port (SP-) VATS is still an intractable problem. In the present study, we reported the surgical results of chronic inflammatory lung disease and shared some useful SP-VATS techniques. METHODS: We retrospectively assessed the surgical results of chronic inflammatory lung disease, primarily bronchiectasis, and mycobacterial infection, at our institution between 2010 and 2018. The patients who underwent SP-VATS anatomic resection were compared with those who underwent MP-VATS procedures. We analyzed the baseline characteristics, perioperative data, and postoperative outcomes, and illustrated four special techniques depending on the situation: flexible hook electrocautery, hilum-first technique, application of Satinsky vascular clamp, and staged closure of bronchial stump method. RESULTS: We classified 170 consecutive patients undergoing thoracoscopic anatomic resection into SP and MP groups, which had significant between-group differences in operation time and overall complication rate (P = 0.037 and 0.018, respectively). Compared to the MP-VATS group, the operation time of SP-VATS was shorter, and the conversion rate of SP-VATS was relatively lower (3.1% vs. 10.5%, P = 0.135). The most common complication was prolonged air leakage (SP-VATS, 10.8%; MP-VATS, 2.9%, P = 0.045). CONCLUSIONS: For chronic inflammatory lung disease, certain surgical techniques render SP-VATS anatomic resection feasible and safe with a lower conversion rate.

Esophageal fistula after definitive concurrent chemotherapy and intensity modulated radiotherapy for esophageal squamous cell carcinoma.

BACKGROUND: The literature regarding esophageal fistula after definitive concurrent chemotherapy and intensity modulated radiotherapy (IMRT) for esophageal squamous cell carcinoma (ESCC) remains lacking. We aimed to investigate the risk factors of esophageal fistula among ESCC patients undergoing definitive concurrent chemoradiotherapy (CCRT) via IMRT technique. METHODS: A total of 129 consecutive ESCC patients receiving definitive CCRT with IMRT between 2008 and 2018 were reviewed. The cumulative incidence of esophageal fistula and survival of patients were estimated by the Kaplan-Meier method and compared between groups by the log-rank test. The risk factors of esophageal fistula were determined with multivariate Cox proportional hazards regression analysis. RESULTS: Median follow-up was 14.9 months (IQR, 7.0-28.8). Esophageal perforation was identified in 20 (15.5%) patients, resulting in esophago-pleural fistula in nine, esophago-tracheal fistula in seven, broncho-esophageal fistula in two, and aorto-esophageal fistula in two patients. The median interval from IMRT to the occurrence of esophageal fistula was 4.4 months (IQR, 3.3-10.1). Patients with esophageal fistula had an inferior median overall survival (10.0 vs. 17.2 months, p = 0.0096). T4 (HR, 3.776; 95% CI, 1.383-10.308; p = 0.010) and esophageal stenosis (HR, 2.601; 95% CI, 1.053-6.428; p = 0.038) at baseline were the independent risk factors for esophageal fistula. The cumulative incidence of esophageal fistula was higher in patients with T4 (p = 0.018) and pre-treatment esophageal stenosis (p = 0.045). There was a trend toward better survival after esophageal fistula among patients receiving repair or stenting for the fistula than those only undergoing conservative treatments (median survival, 5.9 vs. 0.9 months, p = 0.058). CONCLUSIONS: T4 and esophageal stenosis at baseline independently increased the risk of esophageal fistula in ESCC treated by definitive CCRT with IMRT. There existed a trend toward improved survival after the fistula among patients receiving repair or stenting for esophageal perforation.

EGFR-TKI plus bevacizumab versus EGFR-TKI monotherapy for patients with EGFR mutation-positive advanced non-small cell lung cancer-A propensity score matching analysis.

BACKGROUND: Recent study showed that the combination of erlotinib and bevacizumab had better disease control than erlotinib monotherapy in patients with advanced epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC). However, there is lack of real-world evidence for this therapeutic regimen. We aimed to compare outcomes between patients with EGFR mutant NSCLC treated with EGFR-tyrosine kinase inhibitors (TKI) and bevacizumab and those treated with EGFR-TKI alone in a real-world setting. METHODS: Patients with advanced EGFR-mutant NSCLC who received first-line EGFR-TKI in a tertiary referral center from October 1, 2013 to December 31, 2019 were retrospectively analyzed. We performed 1:2 propensity score-matching: one EGFR-TKI and bevacizumab recipient with two patients who received EGFR-TKI alone. Progression-free survival (PFS) and overall survival (OS) were evaluated using the Kaplan-Meier method. The prognostic factors were analyzed using Cox proportional hazards regression analysis. RESULTS: Total 313 patients were enrolled. After propensity score matching, 45 patients who received first-line EGFR-TKI and bevacizumab and 89 patients who received EGFR-TKI alone were analyzed. The combination group showed improved PFS (17.0 vs. 11.0 months; hazard ratio [HR] = 0.48; p = 0.002) compared to the monotherapy group. In subgroup analysis of patients with an L858R mutation, the combination group showed longer PFS (23.1 vs. 10.7 months; HR = 0.40; p = 0.011) and OS (not reached vs. 40.6 months; HR = 0.27; p = 0.040) than the EGFR-TKI monotherapy group. CONCLUSION: Our data suggest that the combination of EGFR-TKI and bevacizumab could improve PFS in patients with EGFR-mutant NSCLC. In patients harboring L858R mutation, the combination therapy provides better OS than TKI alone.

Downstream Complications and Healthcare Expenditure after Invasive Procedures for Lung Lesions in Taiwan.

This study aimed to estimate the downstream complications and healthcare expenditure after invasive procedures for lung lesions, which in turn could be used for future cost-effectiveness analyses of lung cancer screening in Taiwan. We interlinked the Taiwan National Beneficiary Registry with the National Health Insurance Reimbursement databases to identify non-lung cancer individuals aged 50-80 years who underwent invasive lung procedures within one month after non-contrast chest computed tomography between 2014 and 2016. We directly matched one individual with 10 controls by age, gender, calendar year, residence area, comorbidities, and the past one-year healthcare expenditure to calculate incremental one-month complication rates and attributable costs. A total of 5805 individuals who underwent invasive lung procedures were identified and matched with 58,050 controls. The incremental one-month complication rates were 13.4% (95% CI: 10.9% to 15.8%), 10.7% (95% CI: 9.2% to 12.1%), and 4.4% (95% CI: 2.0% to 6.7%) for thoracic surgery, bronchoscopy, and needle biopsy, respectively. The incremental one-month healthcare expenditure for minor, intermediate, and major complications were NT$1493 (95% CI: NT$-3107 to NT$6092), NT$18,422 (95% CI: NT$13,755 to NT$23,089), and NT$58,021 (95% CI: NT$46,114 to NT$69,929), respectively. Individuals aged 60-64 years incurred the highest incremental costs. Downstream complications and the healthcare expenditure after invasive procedures for lung lesions would be substantial for non-lung cancer individuals 50-80 years of age. These estimates could be used in modeling the cost-effectiveness of the national lung screening program in Taiwan.

Stapled video-assisted thoracoscopic segmentectomy preserves as much lung volume as nonstapled video-assisted thoracoscopic segmentectomy.

BACKGROUND: Two different techniques of performing segmentectomy have been reported in the era of video-assisted thoracosopic surgery (VATS), including stapled segmentectomy (SS) and non-stapled segmentectomy (NSS). Some surgeons favor stapled segmentectomy for better pneumostatic control, while others prefer non-stapled segmentectomy to avoid compromising adjacent pulmonary parenchyma. In this study, we used multidetector computed tomography (MDCT) and spirometry to evaluate lung volume preservation of different segmentectomy techniques. METHODS: A total of 269 patients undergoing video-assisted thoracic surgery (VATS) segmentectomy between October 2013 and September 2016 in a single institution were reviewed. Perioperative outcomes, the cost of hospital admission, the change in forced expiratory volume in 1 s (FEV1) (ΔFEV1 and ΔFEV1%), and residual ipsilateral volume ratios (RiVR) were compared. RESULTS: The final study population consisted of 107 patients: 30 patients underwent NSS, and 77 patients underwent SS. The NSS group had significantly longer operative time, more blood loss, longer duration of chest tube placement and postoperative hospitalization than the SS group. The follow-up of RiVR (at 6 months, 12 months, 24 months), ΔFEV1(L), and ΔFEV1(%) demonstrated no significant difference between NSS and SS group. CONCLUSION: Our study demonstrated that postoperative residual lung volume was not influenced by different segmentectomy techniques.

MicroRNA-146a suppresses tumor malignancy via targeting vimentin in esophageal squamous cell carcinoma cells with lower fibronectin membrane assembly.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is widely prevalent in Taiwan, and high metastatic spread of ESCC leads to poor survival rate. Fibronectin (FN) assembly on the cell membrane may induce ESCC mobility. MicroRNAs (MiRNAs) are abundant in and participate in tumorigenesis in many cancers. However, the role of MiRNA in FN assembly-related ESCC mobility remains unexplored. METHODS: We divided ESCC CE81T cells into high-FN assembly (CE81FN+) and low-FN assembly (CE81FN-) groups by flow cytometry. MiRNA microarray analysis identified miR-146a expression as the most down-regulated miRNA in comparison of CE81FN+ and CE81FN- cells. RESULTS: Cell proliferation and migration were decreased when CE81FN+ cells overexpressed transgenic miR-146a compared to the parental cells, indicating an inverse correlation between low miR-146a expression and high proliferation as well as motility of FN assembly ESCC cells. Furthermore, vimentin is the target gene of miR-146a involved in ESCC tumorigenesis. MiR-146a suppressed cell proliferation, migration and invasion of CE81FN+ cells through the inhibition of vimentin expression, as confirmed by real-time PCR, Western blotting and Transwell™ assay. Analysis of one hundred and thirty-six paired ESCC patient specimens revealed that low miR-146a and high vimentin levels were frequently detected in tumor, and that the former was associated with late tumor stages (III and IV). Notably, either low miR-146a expression or high vimentin level was significantly associated with poor overall survival rate among ESCC patients. CONCLUSIONS: This is the first report to link FN assembly in the cell membrane with miR-146a, vimentin and ESCC tumorigenesis both in vitro and in ESCC patients.