Prediction of the stage shift growth of early-stage lung adenocarcinomas by volume-doubling time.

Background: Prediction of subsolid nodule (SSN) interval growth is crucial for clinical management and decision making in lung cancer screening program. To the best of our knowledge, no study has investigated whether volume doubling time (VDT) is an independent factor for predicting SSN interval growth, or whether its predictive power is better than that of traditional semantic methods, such as nodular diameter or type. This study aimed to investigate whether VDT could provide added value in predicting the long-term natural course of SSNs (<3 cm) regarding stage shift. Methods: This retrospective study enrolled 132 patients with spectrum lesions of lung adenocarcinoma who underwent two consecutive computed tomography (CT) examinations before surgical tissue proofing between 2012 and 2021 in Kaohsiung Veterans General Hospital. The VDTs were manually calculated from the volumetric segmentation using Schwartz's approximation formula. We utilized logistic regression to identify predictors associated with stage shift progression based on the VDT parameter. Results: The average duration of follow-up period was 3.629 years. A VDT-based nomogram model (model 2) based on CT semantic features, clinical characteristics, and the VDT parameter yielded an area under the curve (AUC) of 0.877 [95% confidence interval (CI): 0.807-0.928]. Compared with model 1 (CT semantic features and clinical characteristics), model 2 exhibited the better predictive performance for stage shift (AUC model 1: 0.833 versus AUC model 2: 0.877, P=0.047). In model 2, significant predictors of stage shift growth included initial nodule size [odds ratio (OR) =4.074, 95% CI: 1.368-12.135; P=0.012], SSN classification (OR =0.042; 95% CI: 0.006-0.288; P=0.001), follow-up period (OR =1.692, 95% CI: 1.337-2.140; P<0.001), and VDT classification (OR =2.327, 95% CI: 1.368-3.958; P=0.002). For the stage shift, the mean progression time for the VDT (>400 d) group was 7.595 years, and median progression time was 7.430 years. Additionally, a VDT ≤400 d is an important prognostic factor associated with aggressive growth behavior with a stage shift. Conclusions: VDT is crucial for predicting SSN stage shift growth irrespective of clinical and CT semantic features. This highlights its significance in informing follow-up protocols and surgical planning, emphasizing its prognostic value in predicting SSN growth.

A Retrospective Analysis: Investigating Factors Linked to High Lung-RADS Scores in a Nonsmoking, Non-Family History Population.

Low-dose computed tomography screening for lung cancer is currently targeted at heavy smokers or those with a family history of lung cancer. This study aimed to identify risk factors for lung cancer in individuals who do not meet the current lung cancer screening criteria as stipulated by the Taiwan Health Promotion Agency's low-dose computed tomography (LDCT) screening policy. A cohort analysis was conducted on 12,542 asymptomatic healthy subjects aged 20-80 years old who voluntarily underwent LDCT scans from January 2016 to December 2021. Logistic regression demonstrated that several factors, including age over 55 years, female gender, a body mass index (BMI) less than 23, a previous history of respiratory diseases such as tuberculosis or obstructive respiratory diseases (chronic obstructive pulmonary disease [COPD], asthma), and previous respiratory symptoms such as cough or dyspnea, were associated with high-risk lung radiology scores according to LDCT scans. These findings indicate that risk-based assessments using primary data and questionnaires to identify risk factors other than heavy smoking and a family history of lung cancer may improve the efficiency of lung cancer screening.

Managing Persistent Subsolid Nodules in Lung Cancer: Education, Decision Making, and Impact of Interval Growth Patterns.

With the popularization of lung cancer screening, many persistent subsolid nodules (SSNs) have been identified clinically, especially in Asian non-smokers. However, many studies have found that SSNs exhibit heterogeneous growth trends during long-term follow ups. This article adopted a narrative approach to extensively review the available literature on the topic to explore the definitions, rationale, and clinical application of different interval growths of subsolid pulmonary nodule management and follow-up strategies. The development of SSN growth thresholds with different growth patterns could support clinical decision making with follow-up guidelines to reduce over- and delayed diagnoses. In conclusion, using different SSN growth thresholds could optimize the follow-up management and clinical decision making of SSNs in lung cancer screening programs. This could further reduce the lung cancer mortality rate and potential harm from overdiagnosis and over management.

Prediction of Interval Growth of Lung Adenocarcinomas Manifesting as Persistent Subsolid Nodules ≤3 cm Based on Radiomic Features.

RATIONALES AND OBJECTIVES: To investigate the prognostic value of the radiomic-based prediction model in predicting the interval growth rate of persistent subsolid nodules (SSNs) with an initial size of ≤ 3 cm manifesting as lung adenocarcinomas. MATERIALS AND METHODS: A total of 133 patients (mean age, 59.02 years; male, 37.6%) with 133 SSNs who underwent a series of CT examinations at our hospital between 2012 and 2022 were included in this study. Forty-one radiomic features were extracted from each volumetric region of interest. Radiomic features combined with conventional clinical and semantic parameters were then selected for radiomic-based model building. To investigate the model performance in terms of substantial SSN growth and stage shift growth, the model performance was compared by the area under the curve (AUC) obtained by receiver operating characteristic analysis. RESULTS: The mean follow-up period was 3.62 years. For substantial SSN growth, a radiomic-based model (Model 2) based on clinical characteristics, CT semantic features, and radiomic features yielded an AUCs of 0.869 (95% CI: 0.799-0.922). In comparison with Model 1 (clinical characteristics and CT semantic features), Model 2 performed better than Model 1 for substantial SSN growth (AUC model 1:0.793 versus AUC model 2:0.869, p = 0.028). A radiomic-based nomogram combining sex, follow-up period, and three radiomic features was built for substantial SSN growth prediction. For the stage shift growth, a radiomic-based model (Model 4) based on clinical characteristics, CT semantic features, and radiomic features yielded an AUCs of 0.883 (95% CI: 0.815-0.933). Compared with Model 3 (clinical characteristics and CT semantic features), Model 4 performed better than the model 3 for stage shift growth (AUC model 1: 0.769 versus AUC model 2: 0.883, p = 0.006). A radiomic-based nomogram combining the initial nodule size, SSN classification, follow-up period, and three radiomic features was built to predict the stage shift growth. CONCLUSION: Radiomic-based models have superior utility in estimating the prognostic interval growth of patients with early lung adenocarcinomas (≤ 3 cm) than conventional clinical-semantic models in terms of substantial interval growth and stage shift growth, potentially guiding clinical decision-making with follow-up strategies of SSNs in personalized precision medicine.

Impact of Smoking Status on Lung Cancer Characteristics and Mortality Rates between Screened and Non-Screened Lung Cancer Cohorts: Real-World Knowledge Translation and Education.

This was a retrospective hospital-based cohort study of participants diagnosed with lung cancer in the lung cancer register database, and our goal was to evaluate the impact of smoking and screening status on lung cancer characteristics and clinical outcomes. According to the hospital-based lung cancer register database, a total of 2883 lung cancers were diagnosed in 2883 patients between January 2007 and September 2017, which were divided into four groups according to smoking and screening status. A comparison was performed in terms of clinical characteristics and outcomes of lung cancer between the four groups. For non-smokers, age, gender, screened status, tumor size, targeted therapy, and curative surgery were independent prognostic factors of overall survival for lung cancer subjects. However, screened status and gender were not significant prognostic factors for lung cancer survival in smokers with lung cancer. For the non-smoker group, about 4.9% of lung cancer subjects (N = 81) were detected by screening. However, only 0.97% of lung cancer subjects (N = 12) were detected by screening in smokers. This could be attributed to smokers' negative attitudes and low socioeconomic status preventing LDCT lung cancer screening. In summary, our real-world data suggest that effectively encouraging smokers to be more willing to participate in lung cancer screening programs with screening allowance and educational training in the future is an important issue.

Prognostic effect of implementation of the mass low-dose computed tomography lung cancer screening program: a hospital-based cohort study.

Low-dose computed tomography lung cancer screening aims to detect early-stage lung cancers in order to decrease the incidence of advanced-stage lung cancers and to reduce lung cancer mortality. We analyzed the time trends of lung cancer stage distribution and mortality rates after the gradual implementation of the low-dose computed tomography lung cancer screening in a hospital-based cohort. Using the hospital-based cancer registry data on lung cancer number and death from 2007 to 2014, we aim to evaluate the trends in stage distribution and mortality rate after the gradual implementation of low-dose computed tomography lung cancer screening program over recent years. From 2007 to 2014, overall 2542 cases of lung cancers were diagnosed according to hospital-based cancer registry. For the 1-year mortality rate, the mortality rate decreased gradually from 48.16 to 37.04% between 2007 and 2014. For the 5-year mortality rate, the mortality rate decreased gradually from 88.49 to 69.44% between 2007 and 2014. There was a gradual decrease in stage IV lung cancer with the corresponding sharp increase in stage I early lung cancer after following the implementation of the large volume of the low-dose computed tomography examination between the years 2011 and 2014. In conclusion, these results suggest that the gradual implementation of low-dose computed tomography lung screening program could lead to a remarkable decrease in lung cancer mortality and a remarkable stage shift in the trend over time in this hospital-based cohort.

Differences in lung cancer characteristics and mortality rate between screened and non-screened cohorts.

Screening programs for lung cancer aim to allow diagnosis at the early stage, and therefore the decline in mortality rates. Thus, the aim of this retrospective cohort study was to the comparison of screened and non-screened lung cancer in terms of lung cancer characteristics, overdiagnosis and survival rate. A retrospective study in which 2883 patients with 2883 lung cancer diagnosed according to the hospital-based lung cancer register database between 2007 and 2017. A comparison was performed in term of clinical characteristics and outcomes of lung cancer between the screened and non-screening patient groups. 2883 subjects were identified (93 screened and 2790 non-screened). Screened group patients were younger (59.91 ± 8.14 versus 67.58 ± 12.95; p < 0.0001), and were more likely to be female than non-screened group (61.3% versus 36.8%; p < 0.0001). The screened group showed significantly better outcomes in overall mortality than the non-screened group (10.75% versus 79.06%; <0.0001). In a Cox proportional hazard model, lung cancer in the screened group proved to be an independent prognostic factor in lung cancer subjects. Our findings point to the improved survival outcome in the screened group and might underline the benefit of low-dose computed tomography (LDCT) screening program in Asian populations with the high prevalence of non-smoking-related lung cancer. Further study aimed at the LDCT mass screening program targeting at light smokers and non-smoker outside of existing screening criteria is warranted.

Risk factors for Barrett's esophagus in young adults who underwent upper gastrointestinal endoscopy in a health examination center.

BACKGROUND: Barrett's esophagus (BE) is a premalignant condition with increased incidence worldwide both in old and young individuals. However, the role of certain potential risk factors remains unclear in young adults (< 50 years). We aimed to determine the risk factors of BE in young adults. METHODS: A total of 4943 young adults who underwent upper gastrointestinal endoscopy at our health check-up center were enrolled. The diagnosis of BE was based on histological confirmation. We analyzed demographic factors, laboratory data, potential risk factors such as smoking, alcohol consumption, presence of gastroesophageal reflux disease (GERD) symptoms, and metabolic syndrome for the risk of BE by using binary logistic regression analysis. RESULTS: The prevalence of BE was 1.8% (88/4943). Male sex, the presence of GERD symptoms, and smoking were three significant risk factors related to BE. Furthermore, participants who had smoked for 10 pack-years or more had increased risk of BE with dose-dependent phenomenon (p trend < 0.001). The proportion of BE in male participants with both GERD symptoms and a smoking history of 10 pack-years or more was as high as 10.3% (16/155). CONCLUSIONS: Significant risk factors of BE in young adults are male sex, the presence of GERD symptoms, and smoking. The risk also increases with an increase in cumulative exposure to smoking.

Prevalence and risk factors for colonization by extended-spectrum ß-lactamase-producing or ST 131 Escherichia coli among asymptomatic adults in community settings in Southern Taiwan.

Purpose: Fecal carriage of extended-spectrum ß-lactamase-producing Escherichia coli (ESBL-EC) is common in Asia, especially in China and Southeast Asia. There are no data about fecal carriage of ESBL-EC and mcr-1-positive E. coli in Taiwan, and few studies focusing on the risk factors of asymptomatic fecal carriage of epidemic ST131 E. coli have been published. Patients and methods: From healthy inhabitants attending health examinations at a medical center in southern Taiwan in 2017, we collected 724 stool samples, which were examined for ESBL-EC fecal carriage using chromogenic medium. ST131 and mcr1-positive E. coli were also investigated using multiplex PCR. Clinical data from all participating adults were collected to analyze the risk factors for fecal ESBL-EC or ST131 E. coli carriage. Results: The prevalence rate of asymptomatic ESBL-EC fecal carriage in adults was 1.9% (14/724). ST131 was found in 22 (3.0%) adults and mcr-1-positive E. coli was found in three (0.4%) adults. A multivariate analysis showed that the risk factors associated with ESBL-EC carriage were diabetes mellitus (adjusted odds ratio [aOR]: 5.5, 95% confidence interval [CI]: 1.3-22.7), a history of colonic polyps (aOR: 6.4, 95% CI: 1.6-24.9), and chronic renal insufficiency (aOR: 20.7, 95% CI: 1.4-305.7). Underlying cancer (aOR: 4.8, 95% CI: 1.0-22.5) and stroke (aOR: 18.0, 95% CI: 1.6-207.5) were associated with ST131 E. coli fecal carriage. In our cohort, travel to Asian countries and food habit were not associated with ST131 or ESBL-EC fecal carriage. Conclusions: The ESBL-EC or ST131 E. coli fecal carriage rate is low among asymptomatic adults in Taiwan. Certain underlying medical conditions were associated with their fecal carriage.

Role of Fatty Liver Index and Metabolic Factors in the Prediction of Nonalcoholic Fatty Liver Disease in a Lean Population Receiving Health Checkup.

OBJECTIVES: Some metabolic factors and noninvasive markers, including fatty liver index (FLI), are used to predict nonalcoholic fatty liver disease (NAFLD) in obese patients. Despite the increasing prevalence of NAFLD in lean patients (lean-NAFLD), the risk factors and predictors are not well determined in this population. We investigated factors associated with lean-NAFLD and validated their predictive ability. METHODS: From 9,293 examinees who underwent routine health checkups, we enrolled 4,000, aged ≥20 years, with a body mass index <24 kg/m in our lean-NAFLD study population. NAFLD diagnoses were made according to the patients' histories, laboratory values, and sonographic criteria. Clinical variables, serum sugar, lipid, and liver profiles were evaluated using multiple logistic regression analysis. The predictive ability and optimal cutoff values for NAFLD were determined according to the area under the receiver operating characteristic curve. RESULTS: Overall, 18.5% (n = 740) of the lean population had NAFLD. Male sex, body mass index, body fat mass, fasting plasma glucose, uric acid, alanine aminotransferase, triglyceride, and FLI values were associated with NAFLD. FLI had the best discriminative ability to predict lean-NAFLD compared to the other biochemical markers. We further used the Youden index test and found an optimum cut-off value for FLI of 15 with the highest discriminant ability than other values. DISCUSSION: The prevalence of lean-NAFLD was not low. FLI was superior to other predictors including sex, liver function, and other metabolic factors, in the prediction of lean-NAFLD. FLI may be considered an easy to use, noninvasive marker to screen for lean-NAFLD.

Natural History of Persistent Pulmonary Subsolid Nodules: Long-Term Observation of Different Interval Growth.

BACKGROUND: The long-term natural course and outcomes of subsolid nodules (SSNs) in terms of true growth, substantial growth, and stage shift need to be clarified. METHODS: Between 2002 and 2016, 128 subjects with persistent SSNs of 3cm or smaller were enrolled. The baseline and interval changes in the series computed tomography (CT) findings during the follow-up period were subsequently reviewed. RESULTS: The mean follow-up period was 3.57±2.93years. The cumulative percentage of growth nodules of the part-solid nodule (PSN) group was significantly higher than that of the ground-glass nodule (GGN) group by Kaplan-Meier estimation (all p<0.0001). For true SSN growth, GGNs usually take a median follow-up of 7 years to grow; PSNs usually take a median follow-up of 3 years to grow. For substantial SSN growth, GGNs usually take a median follow-up of 9 years to grow; PSNs usually take a median follow-up of 3 years to grow. For stage shift, GGNs usually take a median follow-up of 12 years to grow; PSNs usually take a median follow-up of 9 years to grow. CONCLUSIONS: The natural course in terms of true growth, substantial growth, and stage shift differed significantly according to their nodule type, which could contribute to the development of follow-up guidelines and management strategy of pulmonary SSNs.

Modified Lung-RADS Improves Performance of Screening LDCT in a Population with High Prevalence of Non-smoking-related Lung Cancer.

OBJECTIVES: We proposed a modification of the ACR Lung Imaging Reporting and Data System (Lung-RADS) to clarify the characteristics of subsolid nodules with categories 1-11, and to compare the diagnostic accuracy with Lung-RADS and National Lung Screening Trial criteria in an Asian population with high prevalence of adenocarcinoma. METHODS: We analyzed a retrospective cohort of 1978 consecutive healthy subjects (72.8% nonsmoker) who underwent low-dose computed tomography from August 2013 to October 2014 (1084 men, 894 women). Lung-RADS categories 2 and 3 were modified to include subcategories of 2A/2B/2C and 3A/3B/3C, respectively. Clinical information and nodule characteristics were recorded. Receiver operating characteristic curves were used to compare diagnostic accuracy at different cutoffs. RESULTS: Thirty-two subjects (30 nonsmokers) had pathology-proven adenocarcinoma spectrum lesions in the follow-up period (1.6 ± 0.5 years). Modified Lung-RADS, using modified Lung-RADS category 2C as cutoff, had an area under the curve (AUC) of 0.973 in predicting adenocarcinoma spectrum lesions (sensitivity of 100%, specificity of 89.3%), which was significantly higher than that of Lung-RADS (AUC = 0.815, P < .001) and National Lung Screening Trial (AUC = 0.906, P < .001). Furthermore, modified Lung-RADS showed an AUC of 0.992 in predicting invasive adenocarcinoma (sensitivity of 95%, specificity of 97.8%) when category 3B was used as cutoff. CONCLUSIONS: Modified Lung-RADS may substantially improve sensitivity while maintaining specificity for detection of adenocarcinoma spectrum lesions in an Asian population. Compared to Lung-RADS, it has enhanced ability to differentiate invasive from indolent adenocarcinoma by more refined subclassification of subsolid nodules using two cutoff values of category 2C and 3B. The effect of using modified Lung-RADS in clinical practice must be carefully studied in prospective large cohort studies.

Assessment of Selection Criteria for Low-Dose Lung Screening CT Among Asian Ethnic Groups in Taiwan: From Mass Screening to Specific Risk-Based Screening for Non-Smoker Lung Cancer.

BACKGROUND: The National Lung Screening Trial (NLST) showed low-dose screening chest computed tomography (CT) reduced the lung cancer mortality rate up to 20% in high-risk patients in the United States. We aimed to investigate the impact of applying the NLST eligibility criteria to the population in Taiwan, and to identify additional risk factors to select subjects at risk for lung cancer. PATIENTS AND METHODS: We retrospectively reviewed the medical records of 1763 asymptomatic healthy subjects (age range, 40-80 years) who voluntarily underwent low-dose chest CT (1029 male, 734 female) from August 2013 to August 2014. Clinical information and nodule characteristics were recorded. The results of subsequent follow-up and outcome were also recorded. RESULTS: A total of 8.4% (148/1763) of subjects would have been eligible for lung cancer screening based on the NLST criteria. However, only 1 of these eligible subjects would have a lung cancer detected at baseline. Among the 1615 subjects who did not meet the NLST criteria, the detection rates of lung cancer were 2.6% in women and 0.56% in men. Logistic regression showed that female gender and a family history of lung cancer were the 2 most important predictors of lung cancer in Taiwan (odds ratio, 6.367; P = .003; odds ratio, 3.017; P = .016, respectively). CONCLUSIONS: In conclusion, NLST eligibility criteria may not be effective in screening for lung cancer in Taiwan. A risk-based prediction model based on the family history of lung cancer and female gender can potentially improve the efficiency of lung cancer screening programs in Taiwan.

Turbidity-based assay for polygalacturonic acid depolymerase activity.

A technically simple and inexpensive discontinuous turbidity assay for qualitative and/or quantitative assessments of polygalacturonic acid depolymerase activity is presented. The enzyme reaction is initiated by the addition of enzyme preparation to a reaction mixture containing 0.02% polygalacturonic acid (PGA) in acetate buffer. The progress of the reaction is monitored by terminating aliquots of the reaction mixture (via heat treatment at appropriate times), subsequently adding poly(diallyldimethylammonium chloride) (PDADMAC) for turbidity development (approximately 30 min), and then measuring the turbidity (typically at 420 nm) of the resulting PGA-PDADMAC complex-containing solution. PGA depolymerase activity causes a decrease in the observed turbidity of PGA-PDADMAC-containing solutions because the stability of the interpolyelectrolyte PGA-PDADMAC complex is a function of the degree of polymerization of the PGA. The rate of turbidity change is herein shown to be proportional to a relatively wide range of enzyme concentrations. The assay is demonstrated using a commercial pectinase preparation and tomato fruit extracts.