Ilio-Iliac Arteriovenous Fistula with May-Thurner Syndrome: A Case Report.

An ilio-iliac arteriovenous fistula (AVF) is rare. Common factors leading to ilio-iliac AVF include congenital malformations, iatrogeny, and trauma. There is limited documentation in the literature of cases involving ilio-iliac AVF with May-Thurner syndrome. Here, we present a case of an ilio-iliac AVF with May-Thurner syndrome in an 80-year-old male. CT and angiography confirmed extensive ilio-iliac AVF. Successful endovascular procedures for ilio-iliac AVF were performed using several variable-sized coils and 1400-2000 µm gelatin particles. After embolization, follow-up abdominopelvic CT revealed an improvement in edema in the left leg.

Improving the accuracy of noninvasive prenatal testing through size-selection between fetal and maternal cfDNA.

OBJECTIVES: In general, fetal cfDNA is shorter than maternal cfDNA, and accuracy of noninvasive prenatal testing (NIPT) results can be improved by selecting shorter cfDNA fragments to enrich fetal-derived cfDNA. This study investigated potential improvements in the accuracy of NIPT by performing classification and analysis based on differences in cfDNA size. METHODS: We performed paired-end sequencing to identify size ranges of fetal and maternal cfDNA from 62,374 pregnant women. We then developed a size-selection method to isolate and analyze both fetal and maternal cfDNA, defining fetal-derived cfDNA as less than 150 bp and maternal-derived cfDNA as greater than 180 bp. RESULTS: By implementing size-selection method, the accuracy of NIPT was improved, resulting in an increase in the overall positive predictive value for all aneuploidies from 89.57% to 97.1%. This was achieved by enriching both fetal and maternal-derived cfDNA, which increased fetal DNA fraction while the number of false positives for all aneuploidies was reduced by more than 70%. CONCLUSIONS: We identified the differences in read length between fetal and maternal-derived cfDNA, and selectively enriched both shorter and longer cfDNA fragments for subsequent analysis. Our approach can increase the detection accuracy of NIPT for detecting fetal aneuploidies and reduce the number of false positives caused by maternal chromosomal abnormalities.

Enhancing Lung Cancer Classification through Integration of Liquid Biopsy Multi-Omics Data with Machine Learning Techniques.

Early detection of lung cancer is crucial for patient survival and treatment. Recent advancements in next-generation sequencing (NGS) analysis enable cell-free DNA (cfDNA) liquid biopsy to detect changes, like chromosomal rearrangements, somatic mutations, and copy number variations (CNVs), in cancer. Machine learning (ML) analysis using cancer markers is a highly promising tool for identifying patterns and anomalies in cancers, making the development of ML-based analysis methods essential. We collected blood samples from 92 lung cancer patients and 80 healthy individuals to analyze the distinction between them. The detection of lung cancer markers Cyfra21 and carcinoembryonic antigen (CEA) in blood revealed significant differences between patients and controls. We performed machine learning analysis to obtain AUC values via Adaptive Boosting (AdaBoost), Multi-Layer Perceptron (MLP), and Logistic Regression (LR) using cancer markers, cfDNA concentrations, and CNV screening. Furthermore, combining the analysis of all multi-omics data for ML showed higher AUC values compared with analyzing each element separately, suggesting the potential for a highly accurate diagnosis of cancer. Overall, our results from ML analysis using multi-omics data obtained from blood demonstrate a remarkable ability of the model to distinguish between lung cancer and healthy individuals, highlighting the potential for a diagnostic model against lung cancer.

Advances in methylation analysis of liquid biopsy in early cancer detection of colorectal and lung cancer.

Methylation patterns in cell-free DNA (cfDNA) have emerged as a promising genomic feature for detecting the presence of cancer and determining its origin. The purpose of this study was to evaluate the diagnostic performance of methylation-sensitive restriction enzyme digestion followed by sequencing (MRE-Seq) using cfDNA, and to investigate the cancer signal origin (CSO) of the cancer using a deep neural network (DNN) analyses for liquid biopsy of colorectal and lung cancer. We developed a selective MRE-Seq method with DNN learning-based prediction model using demethylated-sequence-depth patterns from 63,266 CpG sites using SacII enzyme digestion. A total of 191 patients with stage I-IV cancers (95 lung cancers and 96 colorectal cancers) and 126 noncancer participants were enrolled in this study. Our study showed an area under the receiver operating characteristic curve (AUC) of 0.978 with a sensitivity of 78.1% for colorectal cancer, and an AUC of 0.956 with a sensitivity of 66.3% for lung cancer, both at a specificity of 99.2%. For colorectal cancer, sensitivities for stages I-IV ranged from 76.2 to 83.3% while for lung cancer, sensitivities for stages I-IV ranged from 44.4 to 78.9%, both again at a specificity of 99.2%. The CSO model's true-positive rates were 94.4% and 89.9% for colorectal and lung cancers, respectively. The MRE-Seq was found to be a useful method for detecting global hypomethylation patterns in liquid biopsy samples and accurately diagnosing colorectal and lung cancers, as well as determining CSO of the cancer using DNN analysis.Trial registration: This trial was registered at ClinicalTrials.gov (registration number: NCT04253509) for lung cancer on 5 February 2020, https://clinicaltrials.gov/ct2/show/NCT04253509 . Colorectal cancer samples were retrospectively registered at CRIS (Clinical Research Information Service, registration number: KCT0008037) on 23 December 2022, https://cris.nih.go.kr , https://who.init/ictrp . Healthy control samples were retrospectively registered.

Added Value of Structured Reporting for US of the Pediatric Appendix: Additional CT Examinations and Negative Appendectomy.

Purpose: This study aimed to determine the incremental value of using a structured report (SR) for US examinations of the pediatric appendix. Materials and Methods: Between January 2009 and June 2016, 1150 pediatric patients with suspected appendicitis who underwent US examinations of the appendix were included retrospectively. In November 2012, we developed a five-point scale SR for appendix US examinations. The patients were divided into two groups according to the form of the US report: free-text or SR. The primary clinical outcomes were compared between the two groups, including the rate of CT imaging following US examinations, the negative appendectomy rate (NAR), and the appendiceal perforation rate (PR). Results: In total, 550 patients were included in the free-text group and 600 patients in the SR group. The rate of additional CT examinations decreased by 5.3% in the SR group (8.2%, p = 0.003), and the NAR decreased by 8.4% in the SR group (7.8%, p = 0.028). There was no statistical difference in the appendiceal PR (37.6% vs. 48.0%, p = 0.078). Conclusion: The use of an SR to evaluate US examinations for suspected pediatric appendicitis results in lower CT use and fewer negative appendectomies without an increase in appendiceal PR.

Improving CNV Detection Performance in Microarray Data Using a Machine Learning-Based Approach.

Copy number variation (CNV) is a primary source of structural variation in the human genome, leading to several disorders. Therefore, analyzing neonatal CNVs is crucial for managing CNV-related chromosomal disabilities. However, genomic waves can hinder accurate CNV analysis. To mitigate the influences of the waves, we adopted a machine learning approach and developed a new method that uses a modified log R ratio instead of the commonly used log R ratio. Validation results using samples with known CNVs demonstrated the superior performance of our method. We analyzed a total of 16,046 Korean newborn samples using the new method and identified CNVs related to 39 genetic disorders were identified in 342 cases. The most frequently detected CNV-related disorder was Joubert syndrome 4. The accuracy of our method was further confirmed by analyzing a subset of the detected results using NGS and comparing them with our results. The utilization of a genome-wide single nucleotide polymorphism array with wave offset was shown to be a powerful method for identifying CNVs in neonatal cases. The accurate screening and the ability to identify various disease susceptibilities offered by our new method could facilitate the identification of CNV-associated chromosomal disease etiologies.

10-mer and 9-mer WALK Peptides with Both Antibacterial and Anti-Inflammatory Activities.

Natural antimicrobial peptides (AMPs) are multifunctional host defense peptides (HDPs) that are valuable for various therapeutic applications. In particular, natural and artificial AMPs with dual antibacterial immunomodulatory functions emerged as promising candidates for the development of therapeutic agents to treat infectious inflammation. In an effort to develop useful AMP variants with short lengths and simple amino acid composition, we devised a de novo design strategy to generate a series of model peptide isomer sequences, named WALK peptides, i.e., tryptophan (W)-containing amphipathic-helical (A) leucine (L)/lysine (K) peptides. Here, we generated two groups of WALK peptide isomers: W2L4K4 (WALK244.01~WALK244.10) and W2L4K3 (WALK243.01~WALK243.09). Most showed apparent antibacterial activities against both Gram-positive and Gram-negative bacteria at a concentration of approximately 4 µg/mL along with varied hemolytic activities against human red blood cells. In addition, some exhibited significant anti-inflammatory activities without any significant cytotoxicity in macrophages. Collectively, these results suggest that the two selected peptides, WALK244.04 and WALK243.04, showed promise for the development of antibacterial and anti-inflammatory agents.

A Genome-Wide Association Study and Machine-Learning Algorithm Analysis on the Prediction of Facial Phenotypes by Genotypes in Korean Women.

Purpose: Changes in facial appearance are affected by various intrinsic and extrinsic factors, which vary from person to person. Therefore, each person needs to determine their skin condition accurately to care for their skin accordingly. Recently, genetic identification by skin-related phenotypes has become possible using genome-wide association studies (GWAS) and machine-learning algorithms. However, because most GWAS have focused on populations with American or European skin pigmentation, large-scale GWAS are needed for Asian populations. This study aimed to evaluate the correlation of facial phenotypes with candidate single-nucleotide polymorphisms (SNPs) to predict phenotype from genotype using machine learning. Materials and Methods: A total of 749 Korean women aged 30-50 years were enrolled in this study and evaluated for five facial phenotypes (melanin, gloss, hydration, wrinkle, and elasticity). To find highly related SNPs with each phenotype, GWAS analysis was used. In addition, phenotype prediction was performed using three machine-learning algorithms (linear, ridge, and linear support vector regressions) using five-fold cross-validation. Results: Using GWAS analysis, we found 46 novel highly associated SNPs (p < 1×10-05): 3, 20, 12, 6, and 5 SNPs for melanin, gloss, hydration, wrinkle, and elasticity, respectively. On comparing the performance of each model based on phenotypes using five-fold cross-validation, the ridge regression model showed the highest accuracy (r2 = 0.6422-0.7266) in all skin traits. Therefore, the optimal solution for personal skin diagnosis using GWAS was with the ridge regression model. Conclusion: The proposed facial phenotype prediction model in this study provided the optimal solution for accurately predicting the skin condition of an individual by identifying genotype information of target characteristics and machine-learning methods. This model has potential utility for the development of customized cosmetics.

Initial report of extraperitoneal pedicle dissection in deep inferior epigastric perforator flap breast reconstruction using the da Vinci SP

The deep inferior epigastric perforator (DIEP) flap has been widely used for autologous breast reconstruction after mastectomy. In the conventional surgical method, a long incision is needed at the anterior fascia of the rectus abdominis muscle to obtain sufficient pedicle length; this may increase the risk of incisional hernia. To shorten the incision, several trials have investigated the use of endoscopic/robotic devices for pedicle harvest; however, making multiple additional incisions for port insertion and operating in the intraperitoneal field were inevitable. Here, we describe the first case, in which a DIEP free flap was successfully made using the da Vinci SP model. Our findings can help surgeons perform operations in smaller fields with a single port in the extraperitoneal space. Moreover, this method is expected to lead to fewer donor-related complications and faster healing.

Incidence of osteoporosis and ambient air pollution in South Korea: a population-based retrospective cohort study.

BACKGROUND: This study investigated the associations between exposure to ambient air pollutants and the incidence of osteoporosis using the Korean National Insurance Service-National Sample Cohort. METHODS: This nationwide, population-based, retrospective cohort study included 237,149 adults aged ≥40 years that did not have a diagnosis of osteoporosis at baseline between January 1, 2003, and December 31, 2015. Osteoporosis was defined as claim codes and prescriptions of bisphosphonates or selective estrogen receptor modulators at least twice annually. After matching values for PM10, NO2, CO, and SO2 during the 2002-2015 time period and PM2.5 in 2015 with residential areas, the incidence of osteoporosis was analyzed using a Cox proportional hazards regression model according to the quartile of average yearly concentrations of pollutants. RESULTS: Overall 22.2% of the study subjects, 52,601 (male: 5.6%, female: 37.6%) adults in total, were newly diagnosed with osteoporosis and treated. Exposure to PM10 was positively associated with incidence of osteoporosis (Q4: 1798 per 100,000 person-years vs. Q1: 1655 per 100,000 person-years). The adjusted hazard ratio (HR) with 95% confidence interval (CI) of Q4 in PM10 was 1.034 (1.009-1.062). The effect of PM10 on osteoporosis incidence was distinct in females (adjusted sub-HR: 1.065, 95% CI: 1.003-1.129), subjects aged < 65 years (adjusted sub-HR: 1.040, 95% CI: 1.010-1.072), and for residents in areas with low urbanization (adjusted sub-HR: 1.052, 95% CI: 1.019-1.087). However, there was no increase in osteoporosis based on exposure to NO2, CO, SO2, or PM2.5. CONCLUSIONS: Long-term exposure to PM10 was associated with newly diagnosed osteoporosis in Korean adults aged ≥40 years. This finding can aid in policy-making that is directed to control air pollution as a risk factor for bone health.

Useful Ultrasound Findings of Pediatric Patients with Equivocal Results of Appendicitis: Analysis Based on a Structured Report Form.

Purpose: To identify the features that can be used for differentiating appendicitis from non-appendicitis in pediatric patients with equivocal ultrasound (US) results. Materials and Methods: A total of 53 pediatric patients (≤ 18 years old) with equivocal results on US examination for suspected appendicitis between November 2012 and October 2017 were included. US evaluation was conducted based on information retrieved from a predefined structured report form. Then, the likelihood of appendicitis was prospectively classified into five categories. The equivocal results were considered as grade 3 (indeterminate) and grade 4 (probably appendicitis). Results: Of the 53 patients, 25 (47.2%) and 28 (52.8%) were classified into grade 3 and 4 groups, respectively. Among the individual US findings, increased vascularity of the appendiceal wall and peri-appendiceal fat infiltration were independent findings associated with the diagnosis of appendicitis (p = 0.005, p = 0.045, respectively) in the multivariate logistic regression analysis and showed the highest diagnostic accuracy (69.8% and 62.3%, respectively). Conclusion: Increased vascularity within the appendiceal wall and peri-appendiceal fat infiltration were significant predictors of appendicitis in patients with equivocal US findings.

Transcatheter Removal of Bone Cement Embolism in the Right Atrium after Percutaneous Vertebroplasty: The Embolus Broke in Half and Migrated to the Right Pulmonary Artery Intraoperatively.

Bone cement embolism often occurs during percutaneous vertebroplasty. Bone cement pulmonary arterial embolism generally requires no treatment because of the small size and asymptomatic manifestation. Intracardiac bone cement embolisms are rare but associated with a risk of severe complications. Intracardiac bone cement embolisms are mainly removed through open heart surgery. To the best of our knowledge, only three cases of intracardiac bone cement embolisms removed with interventions have been reported. Here, we report another case of successful transcatheter retrieval of a 6-cm-long cement embolism in the right atrium after percutaneous vertebroplasty. The embolus broke in half and migrated to the right pulmonary artery intraoperatively. Using two snares and a filter retrieval device, we advanced from opposite directions. Further, we gently grasped and pulled the fragments of the right pulmonary artery and aligned them in a linear fashion directly into the sheath for uneventful removal.

Useful Ultrasound Findings of Pediatric Patients with Equivocal Results of Appendicitis: Analysis Based on a Structured Report Form

Purpose@#To identify the features that can be used for differentiating appendicitis from non-appendicitis in pediatric patients with equivocal ultrasound (US) results. @*Materials and Methods@#A total of 53 pediatric patients (≤ 18 years old) with equivocal results on US examination for suspected appendicitis between November 2012 and October 2017 were included. US evaluation was conducted based on information retrieved from a predefined structured report form. Then, the likelihood of appendicitis was prospectively classified into five categories. The equivocal results were considered as grade 3 (indeterminate) and grade 4 (probably appendicitis). @*Results@#Of the 53 patients, 25 (47.2%) and 28 (52.8%) were classified into grade 3 and 4 groups, respectively. Among the individual US findings, increased vascularity of the appendiceal wall and peri-appendiceal fat infiltration were independent findings associated with the diagnosis of appendicitis (p = 0.005, p = 0.045, respectively) in the multivariate logistic regression analysis and showed the highest diagnostic accuracy (69.8% and 62.3%, respectively). @*Conclusion@#Increased vascularity within the appendiceal wall and peri-appendiceal fat infiltration were significant predictors of appendicitis in patients with equivocal US findings.

Transcatheter Removal of Bone Cement Embolism in the Right Atrium after Percutaneous Vertebroplasty: The Embolus Broke in Half and Migrated to the Right Pulmonary Artery Intraoperatively

Bone cement embolism often occurs during percutaneous vertebroplasty. Bone cement pulmonary arterial embolism generally requires no treatment because of the small size and asymptomatic manifestation. Intracardiac bone cement embolisms are rare but associated with a risk of severe complications. Intracardiac bone cement embolisms are mainly removed through open heart surgery. To the best of our knowledge, only three cases of intracardiac bone cement embolisms removed with interventions have been reported. Here, we report another case of successful transcatheter retrieval of a 6-cm-long cement embolism in the right atrium after percutaneous vertebroplasty. The embolus broke in half and migrated to the right pulmonary artery intraoperatively. Using two snares and a filter retrieval device, we advanced from opposite directions. Further, we gently grasped and pulled the fragments of the right pulmonary artery and aligned them in a linear fashion directly into the sheath for uneventful removal.

Hypertension Management in Patients with Chronic Kidney Disease in the Post-SPRINT Era

The management of high blood pressure (BP) is crucial for improving outcomes in patients with chronic kidney disease (CKD). The updated Kidney Disease: Improving Global Outcomes 2021 BP guideline proposes treating adults with CKD to a target systolic BP (SBP) of <120 mmHg based on the standardized office BP measurement.This suggestion is largely based on the finding of SPRINT (Systolic Blood Pressure Intervention Trial) that targeting an SBP of <120 mmHg versus <140 mmHg is beneficial for cardiovascular and mortality outcomes, regardless of the patient’s kidney disease status. However, extended follow-up studies of CKD trials showed that intensive versus usual BP control was associated with a lower risk of kidney failure in patients with, but not in those without, proteinuria. Similarly, a recent population-based study in Korea demonstrated that the optimal on-treatment BP for composite cardiorenal and mortality outcomes was left-shifted in adults with CKD, particularly in those with albuminuria, relative to that in patients without CKD. Moreover, in meta-analyses of randomized trials, more intensive versus standard BP control was associated with a lower risk of all-cause mortality in patients with CKD and albuminuria but not in those without CKD. Meanwhile, a 2020 Cochrane review reported that lower BP targets (≤135/85 mmHg), compared with standard targets (≤140/90 mmHg), resulted in a small reduction in cardiovascular events, an increase in other serious adverse events, and no reduction in total serious adverse events. Lowering SBP to <120 mmHg can potentially increase the risk of treatment-related adverse events beyond the cardioprotective benefits, and standardized BP measurement increases the burden on patients and resources.Thus, targeting a BP of <130/80 mmHg with appropriate office BP measurement can be an option in patients with CKD. The presence of albuminuria would need to be additionally considered to determine individualized BP targets.

Antibiotic use in nasal bone fracture: a nationwide population-based cohort study in Korea

Background@#Prophylactic antibiotics are commonly used in craniofacial surgeries. Despite the low risk of surgical site infection after nasal surgery, a lack of consensus regarding the use of antibiotic prophylaxis in the closed reduction of nasal bone fractures has led to inappropriate prescribing patterns. Through this study, we aimed to investigate the status of prophylactic antibiotic use in closed reductions of nasal bone fractures in Korea. @*Methods@#This retrospective cohort study was conducted using data from the National Health Insurance Service-National Sample Cohort of Korea from 2005 to 2015. We analyzed the medical records of patients who underwent closed reduction of nasal bone fractures. The sex, age, region of residence, comorbidities, and socioeconomic variables of the patients were collected from the database. Factors that affect the prescription of perioperative antibiotics were evaluated using multivariate logistic regression analysis. @*Results@#A total of 3,678 patients (mean± standard deviation of age, 28.7± 14.9 years; 2,850 men [77.5%]; 828 women [22.5%]) were included in this study. The rate of antibiotic prescription during the perioperative period was 51.4%. Approximately 68.8% of prescriptions were written for patients who had received general anesthesia. The odds of perioperative prophylactic antibiotic use were significantly higher in patients who received general anesthesia than who received local anesthesia (odds ratio, 1.59). No difference was found in terms of patient age and physician specialty. Second-generation cephalosporins were the most commonly prescribed antibiotic (45.3%), followed by third- and first-generation cephalosporins (20.3% and 18.8%, respectively). In contrast, lincomycin derivatives and aminoglycosides were not prescribed. @*Conclusion@#The findings of this study showed that there was a wide variety of perioperative antibiotic prescription patterns used in nasal bone surgeries. Evidence-based guidance regarding the prescribing of antimicrobial agents for the closed reduction of nasal bone fractures should be considered in future research.

Antibiotic use in nasal bone fracture: a single-center retrospective study

Background@#Prophylactic antibiotics are used to prevent surgical wound infection; however, proper indications must be followed with careful consideration of the risks and benefits, especially in clean or clean-contaminated wounds. Nasal bone fractures are the most common type of facial bone fracture. The most common method for treating nasal bone fracture is closed reduction, which is performed inside the nasal cavity without an incision. The purpose of this study was to determine the need for antibiotic use in the closed reduction of nasal bone fractures. @*Methods@#A retrospective study was conducted using data from the National Insurance Service Ilsan Hospital of the Republic of Korea between 2016 and 2018. The records of patients who underwent closed reduction of nasal bone fracture were reviewed and classified according to sex, age, comorbidities, perioperative antibiotic usage, postoperative complications, nasal packing, anesthesia type, surgeon’s specialty, and operation time. @*Results@#Among the 373 patients studied, the antibiotic prescription rate was 67.3%. Just 0.8% of patients were prescribed preoperative antibiotics only, 44.0% were prescribed postoperative antibiotics only, and 22.5% were prescribed both preoperative and postoperative antibiotics. There were no cases that satisfied the definition of “surgical site infection.” Furthermore, 2.1% of infection-related complications (e.g., mucosal swelling, synechia, and anosmia) occurred only in the antibiotic usage group. The use of nasal packing, anesthesia type, and surgeon’s specialty did not show any difference in infection-related complication rates. @*Conclusion@#According to the study findings, the routine use of perioperative antibiotics is not recommended in uncomplicated nasal bone fracture surgery.

Verrucous carcinoma arising from actinic keratosis: a case report

Verrucous carcinoma (VC) is a rare subtype of squamous cell carcinoma that commonly occurs in the oral cavity. However, VC of the facial skin is relatively rare. We report a case of a 91-year-old woman with VC of the facial skin in the left zygoma area. She was diagnosed with actinic keratosis (4 × 3 cm) of the same site approximately 12 years previously, but declined further treatment. The mass was excised with a minimum of 0.4 cm from gross margins with the result of free from tumor of all margins by frozen section, allowing for primary closure after skin undermining. Basal resection was performed in the preplatysmal plane. The diagnosis of VC was confirmed by histopathological examination. Postoperatively, the wound healed without incident and with no signs of facial nerve injury. To our knowledge, this is the first reported case of VC of facial skin arising from actinic keratosis.

Transcatheter Removal of Bone Cement Embolism in the Right Atrium after Percutaneous Vertebroplasty: The Embolus Broke in Half and Migrated to the Right Pulmonary Artery Intraoperatively

Bone cement embolism often occurs during percutaneous vertebroplasty. Bone cement pulmonary arterial embolism generally requires no treatment because of the small size and asymptomatic manifestation. Intracardiac bone cement embolisms are rare but associated with a risk of severe complications. Intracardiac bone cement embolisms are mainly removed through open heart surgery. To the best of our knowledge, only three cases of intracardiac bone cement embolisms removed with interventions have been reported. Here, we report another case of successful transcatheter retrieval of a 6-cm-long cement embolism in the right atrium after percutaneous vertebroplasty. The embolus broke in half and migrated to the right pulmonary artery intraoperatively. Using two snares and a filter retrieval device, we advanced from opposite directions. Further, we gently grasped and pulled the fragments of the right pulmonary artery and aligned them in a linear fashion directly into the sheath for uneventful removal.

Clinical Utility of Combined Circulating Tumor Cell and Circulating Tumor DNA Assays for Diagnosis of Primary Lung Cancer.

BACKGROUND/AIM: Although it has been suggested that circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) might be used in a complementary manner in lung cancer diagnosis, limited confirmatory data are available. In this prospective study, we evaluated the diagnostic performance of each assay separately and in combination. PATIENTS AND METHODS: From March 2018 to January 2019, patients with suspected primary lung cancer, who underwent routine lung cancer work-up and peripheral blood sampling, were prospectively enrolled in the study. Epithelial cell adhesion molecule and cytokeratin served as markers of CTCs. In terms of ctDNA analysis, single-nucleotide variants were evaluated via next-generation sequencing. RESULTS: We analyzed 111 patients, including 99 with primary lung cancer and 12 with benign pulmonary disease. The median number of CTCs in 10 ml of blood was 3. The most frequently detected single nucleotide variants of ctDNA were TP53, CDKN2A, and EGFR. The diagnostic sensitivity of conventional tumor marker (combination of carcinoembryonic antigen/CYFRA 21-1/neuron-specific enolase) was 66.7%, while those of the ctDNA and CTC assays were 72.7% and 65.7%, respectively. The sensitivity of the CTC/ctDNA combination (95.0%) was significantly greater than those of the CTC (p<0.001), ctDNA (p<0.001), or conventional tumor marker (p<0.001) alone. Subgroup analysis revealed that the sensitivity of the combination assay was greater than those of the CTC or ctDNA assays alone, regardless of tumor stage or histopathology type. CONCLUSION: The CTC/ctDNA combination assay enhanced the sensitivity of primary lung cancer diagnosis. The combination assay strategy may be clinically useful and could enhance the early detection of lung cancer (ClinicalTrials.gov number: NCT03479099).