Background:Patients with pulmonary Mycobacterium avium-intracellulare complex (MAC) disease who cannot receive standard antimicrobial therapy have limited treatment options. Jiinshihoto, a Kampo formula (traditional Japanese herbal medicine) that is effective for chronic cough and depressive symptoms, has not been evaluated in this population. Objective:To evaluate the physical, immunological, and psychiatric effects of Jiinshihoto in patients with pulmonary MAC who were ineligible for standard antimicrobial treatment. Methods:This single-center, open-label, prospective study was conducted from March 2018 to January 2020. Patients who were not eligible for standard treatment for pulmonary MAC disease were enrolled. Jiinshihoto (3.0 g) was administered three times per day for 12 months. The primary endpoints were 3-month changes in chronic obstructive pulmonary disease assessment test (CAT) scores, body weight, and natural killer (NK) cell activity. Secondary endpoints were 3-month changes in self-rating depression scale (SDS) scores. This study was registered in the UMIN-Clinical Trials Registry (UMIN000033590). Results:In total, 24 patients were enrolled. The mean age was 68 years, and 74% were female; the mean body mass index was 19.3 kg/m2. Of these, 23 patients completed the 3-month follow-up. For the primary endpoints at 3 months, no significant changes were observed in CAT scores (from 11.2 to 11.0, P = .87), body weight (from 48.6 to 48.8 kg, P = .32), or NK cell activity (from 42.6% to 43.9%, P = .58). SDS scores showed significant improvement at 3 months (from 42.2 to 38.5, P = .032) and 12 months (from 42.2 to 40.4, P = .034). Conclusion:Jiinshihoto did not improve respiratory symptoms, weight, or NK cell activity in patients with pulmonary MAC ineligible for standard treatment but may be beneficial for depressive symptoms.

Background:Ipilimumab plus nivolumab (I-N) with or without chemotherapy is an established first-line treatment for advanced non-small cell lung cancer (NSCLC). For patients with a large baseline tumor size (BTS), chemotherapy combined with immune checkpoint inhibitors (ICIs) has shown better outcomes compared with ICI monotherapy. However, the specific radiographic size criteria for determining whether to prioritize the CheckMate227 or CheckMate9LA regimen are undefined. Therefore, we evaluated how BTS impacts the efficacy of I-N-based therapy in our cohort. Methods:This multicenter retrospective study was conducted across 19 institutions in Japan. Adult patients with advanced NSCLC with programmed death-ligand 1 (PD-L1) tumor proportion score (TPS) 1-49% who received I-N-based therapy as first-line systemic treatment between January 2018 and March 2022 were included. We excluded patients with EGFR or ALK mutation. Patients were classified into two groups: the I-N group and the I-N-chemo group. Survival outcomes were evaluated based on BTS (≥50 vs. <50 mm). Baseline covariates were obtained from medical records. Results:A total of 87 patients were included: 25 in the I-N group and 62 in the I-N-chemo group. Among patients with BTS ≥50 mm, median progression-free survival (PFS) was 4.0 months [95% confidence interval (CI): 0.7-6.7] in the I-N group and 5.5 months (95% CI: 3.4-8.1) in the I-N-chemo group (P=0.03). Median overall survival (OS) was 8.3 months (95% CI: 1.0-10.7) for I-N and 17.7 months (95% CI: 10.9-not reached) for I-N-chemo (P=0.005). Among patients with BTS <50 mm, there were no statistically significant differences in PFS or OS between the I-N and I-N-chemo groups. Conclusions:Our findings suggest that I-N combined with chemotherapy may be effective treatment for NSCLC patients with a high tumor burden (BTS ≥50 mm). However, given the retrospective nature of this study and the limited subgroup sample sizes, these results should be interpreted with caution.

Enteric-type thymic adenocarcinomas are rare histological variants with limited treatment options. We report the case of a 56-year-old woman with stage IVB enteric-type thymic adenocarcinoma who was treated with lenvatinib. The patient underwent chemoradiotherapy and subsequently received lenvatinib for local recurrence. Despite the patient receiving a low dosage owing to side effects, the size of the recurrent lesions decreased. However, 5 months later, new brain metastases and carcinomatous meningitis developed, and the patient eventually succumbed to cancer. This case suggests that lenvatinib may be an effective treatment for enteric-type adenocarcinomas. However, at low doses, its efficacy may be limited to intracranial lesions.

Anti-programmed cell death-1 (anti-PD-1) therapy has become the standard immunotherapy for patients with advanced non-small cell lung cancer (NSCLC). However, little is known about the organs influenced by PD-1 inhibitors on a patient’s tumor immunity. We examined the changes in lymphoid tissue proliferation before and after PD-1 inhibitor treatment using 3′-deoxy-3′-[18F]-fluorothymidine (18F-FLT) positron emission tomography (PET). This study included 25 patients with advanced NSCLC who underwent 18F-FLT PET before and 2 and 6 weeks after the initiation of PD-1 inhibitor treatment. We determined the average standardized uptake value (SUVmean) in the spleen, maximum SUV (SUVmax) in the lymph nodes, and the SUVmax, SUVmean, proliferative vertebral volume (PVV), and total vertebral proliferation (TVP) in the thoracolumbar vertebral bodies using 18F-FLT PET and blood test data. The relationship between the rate of change in these parameters before and after treatment and the tumor response was evaluated. The baseline 18F-FLT accumulation in the lymphoid tissues or blood test data between the progressive disease (PD) and non-PD groups were not significantly different. In the spleen and lymph nodes, changes in 18F-FLT accumulation from baseline to 2 or 6 weeks did not differ between the non-PD and PD groups. However, mediastinal lymph node accumulation tended to increase transiently at week 2 compared to that before treatment initiation (median SUVmax 2.19 vs. 2.64, P = 0.073). Regarding changes in vertebral accumulation in the non-PD group, the SUVmax, and PVV were significantly lower at weeks 2 and 6. In the percent changes in 18F-FLT accumulation of the vertebrae after the treatment initiation, the PD group was significantly higher than the non-PD group at the 6-week evaluation (median ΔTVP0-6, 17.0

Dipeptidyl peptidase-4 inhibitors (DPP-4is) are shown to be associated with the development of bullous pemphigoid (BP). Immune checkpoint inhibitors (ICIs) can lead to BP development. Therefore, the combination of DPP-4is and ICIs may predispose an individual to developing BP; however, few reports have focused on this issue. We herein report two patients with non-small-cell lung cancer complicated by diabetes mellitus (DM) who developed BP while receiving DPP-4is and ICIs. The clinical course of these patients suggests that the combination of DPP-4is and ICIs may carry a potential risk of BP development.

INTRODUCTION:Recent studies have suggested enhanced therapeutic effects of subsequent chemotherapy after immune checkpoint inhibitor (ICI) treatment, highlighting the importance of subsequent treatment selection. Nanoparticle albumin-bound paclitaxel (nab-PTX) is commonly used in subsequent chemotherapies; however, its efficacy as a subsequent treatment after ICI treatment has not been reported. METHODS:We retrospectively evaluated the efficacy and safety of nab-PTX using two prospective studies that we previously reported. The first study evaluated the efficacy and safety of nab-PTX as a second-line treatment after the failure of the first-line cytotoxic chemotherapy, excluding ICI (study 1; n = 32), and the other as a subsequent treatment after failure of ICI treatment, regardless of treatment line (study 2; n = 29). RESULTS:The objective response rate was significantly higher in study 2 {55.2% (95% confidence interval [CI]: 28.1-79.6)} than in study 1 (28.1% [95% CI: 13.7-46.7]) (p = 0.04). Although the disease control rate was slightly higher in study 2 (86.2% [95% CI: 65.9-97.0]) than in study 1 (71.9% [95% CI: 53.3-86.3]), there was no significant difference (p = 0.2). The median progression-free survival was significantly longer in study 2 than in study 1 (3.9 months [95% CI: 2.0-5.5] in study 1 vs. 5.6 months [95% CI: 3.0-12.8] in study 2; hazard ratio [HR]: 0.46 [95% CI: 0.27-0.81], p = 0.006). The median overall survival was slightly longer in study 2 despite the greater number of patients who received nab-PTX in late treatment line, but there was no significant difference between study 1 and study 2 (10.9 months [95% CI: 5.1-16.8] in study 1 vs. 11.9 months [95% CI: 7.6-24.8] in study 2; HR: 0.77 [95% CI: 0.46-1.31], p = 0.34). Safety profiles did not differ between the patients in studies 1 and 2. CONCLUSION:Nab-PTX monotherapy may be an effective subsequent treatment option after ICI treatment.

Background/Aim: The efficacy of cytotoxic chemotherapy has been reported to improve after immune checkpoint inhibitor (ICI) administration. We previously conducted a multicenter prospective clinical study to evaluate the efficacy and safety of nanoparticle albumin-bound paclitaxel (nab-PTX) after ICI treatment. In that study, some patients showed a long-term response to nab-PTX, which is not usually observed with singleagent chemotherapy. The present study aimed to evaluate the clinical characteristics of these patients. Patients and Methods: We retrospectively analyzed updated data from 29 patients enrolled in our clinical study who received nab-PTX monotherapy after ICI treatment. We defined a "long-term responder" as a patient who achieved a 1-year progression-free survival (PFS). Results: Among the 29 patients, 10 (34.5%) were long-term responders, two of whom achieved a 5-year PFS. A key difference between long-term and non-long-term responders was that the long-term responders had a significantly higher performance status of 0 (70.0% versus 10.5%; p=0.002). Furthermore, median cycles of previous ICIs and median treatment cycles were significantly higher in long-term responders than in non-long-term responders (8 cycles versus 3 cycles; p=0.03) (5.9 months versus 2.0 months; p=0.02). In the 10 long-term responders, six patients required at least a onestage dose reduction owing to adverse events, and four patients administration after ICI treatment may elicit a long-term response. A long-term response can be achieved even with a dose reduction due to adverse events.

Introduction: Immune checkpoint inhibitors (ICIs) plus chemotherapy is now a standard treatment for non-small cell lung cancer (NSCLC). Whether ICI plus chemotherapy (ICI-chemo) or ipilimumab plus nivolumab (I-N)-based therapy is superior for patients with NSCLC with a programmed death-ligand 1 (PD-L1) tumor proportion score (TPS) of 1-49 % has not been evaluated. Methods: This multicenter retrospective study included NSCLC patients with a TPS score of 1-49 %, who began first-line chemotherapy. Propensity score matching analysis was used to adjust for various confounders and evaluate treatment efficacy. Results: A total of 401 patients were enrolled, of whom 308 received ICI-chemo and 93 received I-N-based therapy. The median OS was 21.0 months in the ICI-chemo group and 20.0 months in the I-N-based therapy group. After propensity score matching, there was no difference in OS or PFS between the ICI-chemo group and the I-N-based therapy group (OS: hazard ratios (HR), 0.83; 95 % confidence interval [CI], 0.54-1.26, PFS: HR, 0.72; 95 % CI, 0.52-1.00). Among PD-L1 TPS 25-49 %, there was a tendency for OS to be favorable for the ICI-chemo group (OS: HR, 0.30; 95 % CI, 0.09-0.85). Treatment discontinuation occurred for 26.2 % of the patients in the ICI-chemo group and 41.9 % in the I-N-based therapy group. Conclusions: Among PD-L1 TPS 1-49 %, there was no significant difference in survival outcomes between the ICI-chemo group and the I-N-based therapy group. Based on the results of a subgroup analysis, ICI-chemo may be superior for treating NSCLC with a TPS of 25-49 %.

8550 Background: Nowadays,immune checkpoint inhibitor (ICI) plus chemotherapy is a standard treatment for non-small cell lung cancer (NSCLC) without targetable oncogene alternations. Recently, ipilimumab plus nivolumab-based therapies (CM227 or CM9LA) are also used as standard treatments for NSCLC. Whether ICI plus chemotherapy (ICI-chemo) or ipilimumab plus nivolumab-based therapy (I-N) is better for patients with NSCLC with PD-L1 tumor proportion score (TPS) 1-49% has not been investigated. Here, we report the results of real-world data in NSCLC patients with PD-L1 TPS 1-49%. Methods: We conducted a multicenter (19 centers in Japan) retrospective cohort study. NSCLC patients with PD-L1 TPS 1-49% who received ICI-chemo or I-N as first-line systemic therapy between January 2018 and March 2022 were eligible. Patients with major epidermal growth factor receptor mutations or anaplastic lymphoma kinase rearrangements were excluded. Results: A total of 401 patients were enrolled: median (range) age 69 (35-90) years; 322 (80.3%) male; ECOG PS 0-1, 372 (92.7%); PS ≥2, 29 (7.3%); 233 (58.1%) adenocarcinoma; PD-L1 TPS 1-24%, 312 (77.8%); 25-49%, 82 (20.4%); 1-49% (details are unknown), 7 (1.8%); ICI-chemo 308 (76.8%); I-N, 93 (23.2%). The median overall survival (OS) was 21.0 months (95%CI, 16.7–27.5) in the ICI-chemo group and 20.0 months (95%CI, 15.1–not reached) in the I-N therapy group, respectively. After propensity score matching, there were no differences in OS and progression-free survival (PFS) between ICI-chemo group (n=92) and I-N group (n=92) (OS: HR, 0.83; 95% CI, 0.54-1.26; p=0.38, PFS: HR, 0.72; 95% CI, 0.52-1.00; p=0.05). Among patients with PD-L1 TPS 25-49%, there was a tendency for better OS in the ICI-chemo group (OS: HR, 0.30; 95% CI, 0.09–0.85, p=0.02). In contrast, among PD-L1 TPS 1-24%, significant difference in OS was not observed. Regarding safety, treatment discontinuation due to adverse events was observed 26.2% in the ICI-chemo group and 41.9% in the I-N group. Treatment related death was seen in 4.5% of the ICI-chemo group and in 3.2% of the I-N group. Pneumonitis was seen in 13.9% of the ICI-chemo group and in 17.6% of the N-I group. Conclusions: In real-world data for NSCLC with PD-L1 TPS 1-49%, there were no significant differences in both OS and PFS between ICI-chemo group and I-N group. Toxicity discontinuation rate was higher in I-N group. Based on the subgroup-analysis results, ICI-chemo might be better for NSCLC with PD-L1 TPS 25-49%. Clinical trial information: UMIN000016441.

Background Although transbronchial diagnostic procedures are sometimes difficult to perform because of the patient’s respiratory or general conditions, endoscopic ultrasound with bronchoscope-guided fine-needle aspiration (EUS-B-FNA), a known transesophageal diagnostic procedure, might be useful for such cases. We conducted this prospective three-center observational study to evaluate the safety and efficacy of EUS-B-FNA in suspected lung cancer patients with poor respiratory or general conditions. Methods Patients with suspected lung cancer with respiratory failure, Eastern Cooperative Oncology Group performance status of 2 or higher, or severe respiratory symptoms, were enrolled. The primary endpoints were the diagnostic yield of lung cancer and its safety, and the secondary endpoints were the success rate of molecular and programmed death ligand 1 (PD-L1) analyses, and the 6-month survival rate in patients with lung cancer. Results We enrolled 30 patients, of which 29 were included in the analysis. Among them, 26 were eventually diagnosed with lung cancer. The diagnostic yield for lung cancer was 100% (26/26). There were no adverse events associated with EUS-B-FNA requiring procedure discontinuation. The success rates of molecular analysis for EGFR , ALK , ROS-1 , and BRAF were 100% (14/14), 100% (11/11), 100% (9/9), and 75% (6/8), respectively. The success rate of the PD-L1 analysis was 100% (15/15). The 6-month survival rate in patients with lung cancer was 53.8% (95% confidence interval [CI]: 33.4–76.4), and the median overall survival (OS) was 196 days (95% CI: 142–446). Conclusions EUS-B-FNA is a safe and effective diagnostic method, even in patients with suspected lung cancer with poor respiratory or general conditions. Trial registration This clinical trial was registered at https://www.umin.ac.jp/ctr/index.htm (UMIN000041235, approved on 28/07/2020).

Purpose For patients with locally advanced non-small-cell lung cancer (LA-NSCLC) that progressed after definitive chemoradiotherapy (CRT) and durvalumab consolidation therapy, no subsequent standard treatment exists. The type of treatment selected for each timing of disease progression and its efficacy have not been investigated. Methods We retrospectively enrolled patients with LA-NSCLC or inoperable NSCLC that progressed after definitive CRT and durvalumab consolidation therapy at 15 Japanese institutions. Patients were classified into the following: Early Discontinuation group (disease progression within 6 months after durvalumab initiation), Late Discontinuation group (disease progression from 7 to 12 months after durvalumab initiation), and Accomplishment group (disease progression from 12 months after durvalumab initiation). Results Altogether, 127 patients were analyzed, including 50 (39.4%), 42 (33.1%) and 35 (27.5%) patients from the Early Discontinuation, Late Discontinuation, and Accomplishment groups, respectively. Subsequent treatments were Platinum plus immune checkpoint inhibitors (ICI) in 18 (14.2%), ICI in 7 (5.5%), Platinum in 59 (46.4%), Non-Platinum in 35 (27.6%), and tyrosine kinase inhibitor in 8 (6.3%) patients. In the Early Discontinuation, Late Discontinuation, and Accomplishment groups, 4 (8.0%), 7 (16.7%), and 7 (20.0%) patients were receiving Platinum plus ICI; 21 (42.0%), 22 (52.4%), and 16 (45.7%) were receiving Platinum, and 20 (40.0%), 8 (19.0%), and 7 (20.0%) were receiving Non-Platinum, respectively. No significant difference in progression-free survival was observed in the timing of disease progression. Conclusion In patients with LA-NSCLC hat progressed after definitive CRT and durvalumab consolidation therapy, subsequent treatment may change depending on the timing of disease progression.

Background: Whether immunotherapy improves the efficacy or worsens adverse events of subsequent chemotherapy remains unclear. We performed a Phase 2 study to evaluate the efficacy and safety of nanoparticle albumin-bound paclitaxel (nab-paclitaxel) as a treatment for advanced non-small cell lung cancer (NSCLC) after treatment with programmed cell death 1 or programmed death ligand 1 [PD-(L)1] inhibitor failure.Methods: Nab-paclitaxel (100 mg/m(2)) was administered on Days 1, 8, and 15 of a 28-day cycle to patients with advanced NSCLC within 12 weeks after the failure of PD-(L)1 inhibitor treatment. The primary endpoint was objective response rate (ORR) in all patients; the secondary endpoints were disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety.Results: Thirty cases were registered, and 29 cases were included in the analysis. The ORR was 55.2% (95% confidence interval [CI]: 28.1%-79.6%) and the DCR was 86.2% (95% CI: 65.9%-97.0%). The median PFS was 5.6 months (95% CI: 4.4-6.7 months), and PFS rates at 1- and 2-year timepoints were 34.5% and 13.3%, respectively. The median OS was 11.9 months (95% CI: 0.8-23.0 months). Good performance status and responder of previous PD-(L)1 inhibitor therapy were independent predictors of PFS. Grade 3 or higher toxicities included leukopenia (27.6%), neutropenia (31.0%), peripheral sensory neuropathy (6.9%), increased alanine aminotransferase and aspartate aminotransferase levels (3.4%), and interstitial lung disease (3.4%).Conclusions: Nab-paclitaxel therapy improved ORR after PD-(L)1 inhibitor treatment failure with a durable response of 13% and acceptable toxicities in patients with advanced NSCLC.

Background Evidence for use of second-line immunosuppressants for immune-related adverse events (irAEs) is inadequate. Therefore, a multicenter analysis should assess the efficacy of second-line immunosuppressants for severe irAEs associated with different malignant diseases. Methods This descriptive study aims to investigate the effects of second-line immunosuppressants on corticosteroid-refractory irAEs in patients with lung cancer. We analyzed the effects of second-line immunosuppressants on underlying lung cancer and associated adverse effects. Results Our study included 4589 patients who had received immune checkpoint inhibitor treatment, with 73 patients (1.6%) developing irAEs requiring second-line immunosuppressants. The most commonly observed irAE was pneumonitis (26 patients), followed by hepatobiliary disorders (15 patients) and enteritis (14 patients). We found a confirmed response rate of 42.3% for pneumonitis, which was lower than the response rates of 86.7% for hepatobiliary disorders and 92.9% for enteritis. The time from the start of corticosteroid therapy to the addition of a second-line immunosuppressant correlated significantly with the resolution of irAE to Grade 1 (correlation coefficients of r = 0.701, p < 0.005). The median progression-free survival and duration of response of underlying lung cancer from second-line immunosuppressant administration were 2.1 and 3.0 months, respectively. Of the patients with irAE, 27.4% developed infections and 5.5% might die due to infection. Conclusion Second-line immunosuppressant response was confirmed in 72.2% of irAEs in patients with lung cancer, with lower response rates observed in irAE pneumonitis compared to other irAEs.

Abstract Background: In Japan, pulmonary Mycobacterium avium-intracellulare complex (MAC) disease is highly prevalent. This study aimed to evaluate the efficacy of Jiinshihoto (JST) for treating pulmonary MAC disease. Methods: Twenty-four patients, not receiving standard treatment for pulmonary MAC disease, were enrolled in this study; of these, 21 patients (3 patients dropped out of the study) were eligible and selected to participate. They were administered JST (3.0 g; Tsumura Co., Tokyo, Japan) three times per day for 12 months. Their weight, chronic obstructive pulmonary disease assessment test (CAT) score, NK cell activity, chest computed tomography (CT) results, blood sample results, Self-rating Depression Scale (SDS) scores, and State-Trait Anxiety Inventory (STAI) scores were measured: (i) before JST administration, (ii) after 3 months, and (iii) at the end of the study. Results: Before JST administration, the exacerbation group (n = 10 patients; 6 patients with worsened conditions at the end of the study and 4 patients who were switched to standard treatment during the study because of exacerbation) had a significantly low body mass index (BMI), mild depression, and high anxiety. The overall patient population showed no significant differences in the chronic obstructive pulmonary disease assessment score, body weight, or natural killer cell activity after 3 months of treatment; however, the SDS score improved significantly. At the end of treatment, the nutritional scores had worsened, but the SDS score improved significantly. Specifically, the SDS scores improved significantly only in the non-exacerbation group (n = 11 patients), and natural killer cell activity improved in the non-exacerbation group. Additionally, a comparison of the data of both groups before and after JST administration showed that the exacerbation group had significantly lower BMI and worse CT scores when using a BMI cutoff of 18.4 (sensitivity, 81.8%; specificity, 70%). Conclusion: Patients with a high BMI and low CT score at the time of initial diagnosis may benefit from JST treatment, which may significantly improve depression and immunity and prevent disease progression. Therefore, JST may be an effective treatment in selected pulmonary MAC patients.Trial registration: This study has been registered in the UMIN-Clinical Trials Registry (UMIN000033590, August 1, 2018).

underwent CT guided biopsy which was inconclusive and started on anti koch's treatment.However his symptoms persisted and he was referred to our center in view of lymphoma or tuberculosis, and we proceeded with EBUS-TBNA.Results: Histopathologic examination of the slides revealed sinus histiocytosis and EMPERIPOLESIS which is specific for Rosai-Dorfman disease. Conclusion:The diagnosis of every lymphadenopathy should be re-instated by a tissue diagnosis.Our case is unique and rare as there are only 4 cases of mediastinal lymphadenopathy reported as Rosai-Dorfman disease and our patient presented with isolated mediastinal lymphadenopathy, when all other reported cases had cervical and axillary lymph node also as presentation.

Background Drug-induced pneumonia (d-pneumonia) and bacterial pneumonia (b-pneumonia) are often difficult to differentiate; therefore, this study examined the possibility of differentiating them using serum biomarkers. Methods The study included 22 and 16 patients diagnosed with b- and d-pneumonia, respectively, at our institution or affiliated institutions. For d-pneumonia, the causative drug was minocycline hydrochloride in four patients, gefitinib in two patients, nivolumab in two patients, pembrolizumab in two patients, sulfasalazine in two patients, loxoprofen in one patient, Bouiougitou in one patient, edoxaban tosilate hydrate in one patient, and abemaciclib in one patient. White blood cell (WBC), C-reactive protein (CRP), Krebs von den Lungen-6 (KL-6), surfactant protein (SP)-D, and SP-A levels were measured in each patient and compared between the groups. Results Significant differences were noted in the WBC and SP-D levels between the two groups (P < 0.05, P < 0.001), but not in the CRP, KL-6, or SP-A levels. Conclusion The study results suggest that SP-D is a useful marker for differentiating b-pneumonia and d-pneumonia.

Background: Bronchoalveolar lavage (BAL) is supposed to be useful for the diagnosis of diffuse lung diseases. Many facilities in Japan usually rinse with physiological saline 3 times 50 ml, but the processing methods of samples are various in each facility. The bronchoalveolar lavage fluid (BALF) collected at each time was analyzed separately (Fraction (Fr.)1-3) and then all were mixed and analyzed (Total). Total was calculated by multiplying the number of cells up to Fr.1-3 by the amount recovered, multiplying each fraction, and summing it up and dividing by the total number of cells. We compared the groups of Fr.1-3 and Total, with Lym > 20%, Neu > 10%, and Eo > 25% (3%) as abnormal values and determined that cases where the diagnosis changed between Fr.3 and Total are different evaluation. Results: In the comparison between Fr.3 and Total, 401 / 2774 cases (13%) showed different evaluation. In total, rate of Macrophage and Lymphocyte were significantly lower and those of Neutrophil and Eosinophil were significantly higher than in Fr.3. In total, rate of Neutrophil and Eosinophil were significantly higher in Fr.1, which might be an airway component. Conclusion: When BALF was evaluated using Total, the results might show wrong evaluation of airway disease, such as chronic airway infection and eosinophilic airway disease. BALF with Fr.3 alone was suggested to reveal accurate evaluation.

BACKGROUND/AIM:Clusters of circulating tumor cells (CTCs) increase metastatic potential compared to single CTC. However, conventional technologies have been unable to generate an accurate analysis of single and cluster CTCs in the peripheral blood. We propose an effective strategy to detect and isolate both single and cluster CTCs using two size-selective microfilters.MATERIALS AND METHODS:Five ml of whole blood were collected from 10 patients with epidermal growth factor receptor mutation-positive non-small cell lung cancer. Single and cluster CTCs were identified using precision microfiltration membranes with two distinct pore sizes together with anti-EpCAM antibody labeling.RESULTS:Single and cluster CTCs were detected by simultaneously using two size-selective microfilters. The EGFR-L858R mutation was detected in the DNA from cells captured using both microfilters.CONCLUSION:Our method can be used to detect and isolate single and cluster CTCs in the whole blood and may facilitate the development of a liquid biopsy strategy.