Objective: To quantitatively analyze and compare the forces and moments generated by thermoformed polyethylene terephthalate glycol (PETG) and direct-printed TC-85 clear aligners (CAs), with various margin designs, during premolar rotation. Methods: In total, 132 CAs were fabricated and divided into four groups (n = 33 per group). Group C consisted of thermoformed PETG aligners with a 2 mm gingival margin. Group E comprised direct-printed TC-85 aligners with equi-gingival margin, whereas Group G utilized direct-printed TC-85 aligners with 2 mm gingival margins.Finally, Group T featured direct-printed TC-85 aligners with an additional 1 mm thickness at the mesial embrasure. The forces and moments were measured using a 6-axis force/moment transducer at 2°, 3°, and 4° of rotation. All measurements were conducted at 37°C to simulate intraoral conditions. Forces were measured in the buccolingual, anteroposterior, and vertical directions, while moments were measured in the mesiodistal, buccolingual, and rotational planes. Results: The PETG aligners (Group C) showed significantly increased buccal and posterior force across the rotation angles (P < 0.05), whereas the intrusive force remained consistent. In contrast, the TC-85 aligners maintained consistent forces across all rotation angles.Direct-printed aligners demonstrated significantly lower intrusive forces than PETG aligners (P < 0.001). Group T exhibited reduced unwanted forces while maintaining effective rotational moments. Furthermore, all direct-printed aligners showed more predictable force delivery patterns than thermoformed aligners. Conclusions Direct-printed TC-85 aligners demonstrated superior force consistency and reduced unwanted side effects compared with traditional PETG aligners. Although marginal design modifications did not significantly improve rotational efficiency, they effectively reduced unwanted intrusive forces.

Background: Small cell lung cancer (SCLC) is called ‘smoker’s disease’ because it is strongly associated with smoking and most cases occur in smokers. However, it can also occur in never smokers. We investigated the clinical features of never smokers with SCLC and compared their treatment outcomes with those of smokers with SCLC. Methods: We retrospectively reviewed the clinical data of patients who had proven SCLC and had received chemotherapy at a single cancer center between July 2002 and April 2021. Results: Of 1,643 patients, 1,416 (86.2%) were enrolled in this study. A total of 162 (11.4%) and 1,254 (88.6%) patients were never smokers and smokers, respectively. There were more female never smokers than smokers (n=130; 80.2% vs. 79, 6.3%, p=0.000), and the incidence of ischemic heart disease was lower among never smokers than among smokers (4/1,416, [2.5%] vs. 83/1,416 [6.6%], p=0.036). Never smokers showed less symptoms at diagnosis than smokers (80.9% vs. 87.2%, p=0.037); however, they showed more toxicity after first-line treatment (61.7% vs. 47.8%, p=0.001). The objective response rate (ORR) was significantly higher in never smokers (74.1% vs. 59.6%, p=0.000). In the multivariate analysis, never smoking and second-line treatment were associated with a better ORR. However, progression-free survival and overall survival were not significantly different between never smokers and smokers. Conclusion In conclusion, never smokers accounted for 11.4% of patients with SCLC. They had distinguishing clinical characteristics and showed better chemotherapeutic responses than smokers.

Background/Aims: Fexuprazan, a novel potassium-competitive acid blocker, was developed for treating acid-related disorders. Pharmacokinetic and pharmacodynamic properties of fexuprazan, unlike those of proton pump inhibitors, are independent of food effect. This study aims to evaluate differences in efficacy and safety of fexuprazan in patients with erosive esophagitis (EE) according to the timing of dosing. Methods: In this multicenter, open-label noninferiority study, patients who had typical reflux symptoms with endoscopically confirmed EE were randomized 1:1 to receive fexuprazan 40 mg daily 30 minutes before or after meal. Treatment was completed after 2 weeks or 4 weeks when healing was endoscopically confirmed. The primary endpoint was the proportion of patients with healed EE confirmed by endoscopy up to week 4. Safety endpoints included treatment-emergent adverse events (TEAEs). Results: In the prior-to-meal group (n = 89) and after-meal group (n = 86), 4-week EE healing rates were 98.77% and 100.00% (difference, 0.01%; 95% CI, –0.01% to 0.04%) and 2-week EE healing rates were 95.77% and 97.14% (difference, 0.01%; 95% CI, –0.05% to 0.07%), respectively. TEAEs were 9.78% and 8.70% in the prior-to-meal group and the after-meal group, respectively. Conclusions Non-inferiority analysis revealed that taking fexuprazan after meal was non-inferior to taking fexuprazan before meals in patients with EE. The frequency of adverse events was similar between the 2 study groups. The drug is safe and effective for healing EE regardless of the timing of dosing.

Purpose: Considering the high disease burden and unique features of Asian patients with breast cancer (BC), it is essential to have a comprehensive view of genetic characteristics in this population. An institutional targeted sequencing platform was developed through the Korea Research-Driven Hospitals project and was incorporated into clinical practice. This study explores the use of targeted next-generation sequencing (NGS) and its outcomes in patients with advanced/metastatic BC in the real world. Materials and Methods: We reviewed the results of NGS tests administered to BC patients using a customized sequencing platform—FiRST Cancer Panel (FCP)—over 7 years. We systematically described clinical translation of FCP for precise diagnostics, personalized therapeutic strategies, and unraveling disease pathogenesis. Results: NGS tests were conducted on 548 samples from 522 patients with BC. Ninety-seven point six percentage of tested samples harbored at least one pathogenic alteration. The common alterations included mutations in TP53 (56.2%), PIK3CA (31.2%), GATA3 (13.8%), BRCA2 (10.2%), and amplifications of CCND1 (10.8%), FGF19 (10.0%), and ERBB2 (9.5%). NGS analysis of ERBB2 amplification correlated well with human epidermal growth factor receptor 2 immunohistochemistry and in situ hybridization. RNA panel analyses found potentially actionable and prognostic fusion genes. FCP effectively screened for potentially germline pathogenic/likely pathogenic mutation. Ten point three percent of BC patients received matched therapy guided by NGS, resulting in a significant overall survival advantage (p=0.022), especially for metastatic BCs. Conclusion Clinical NGS provided multifaceted benefits, deepening our understanding of the disease, improving diagnostic precision, and paving the way for targeted therapies. The concrete advantages of FCP highlight the importance of multi-gene testing for BC, especially for metastatic conditions.

Purpose: It is well known that the majority of the extranodal marginal zone lymphomas of mucosa-associated lymphoid tissues (MALT lymphomas) are associated with microbiota, e.g., gastric MALT lymphoma with Helicobacter pylori. In general, they are very sensitive to low-dose radiotherapy and chemotherapeutic agents. The microbiota profile is not clearly elucidated in bronchus-associated lymphoid tissue (BALT) lymphoma, a rare type of MALT lymphoma in the lung. Thus, this study aimed to clarify the intratumor microbiome in BALT lymphoma using the third-generation next-generation sequencing (NGS) method. Materials and Methods: DNAs were extracted from 12 formalin-fixed paraffin-embedded (FFPE) tumor tissues obtained from BALT lymphoma patients diagnosed between 1990 and 2016. 16S rRNA gene was amplified by polymerase chain reaction. Amplicons were sequenced using a Nanopore platform. Next-generation sequencing analysis was performed to assess microbial profiles. For comparison, FFPE specimens from nine non-cancerous lung tissues were also analyzed. Results: Specific bacterial families including Burkholderiaceae, Bacillaceae, and Microbacteriaceae were associated with BALT lymphoma by a linear discriminant analysis effect size approach. Although the number of specimens was limited, BALT lymphomas exhibited significantly higher microbial abundance and diversity with distinct microbial composition patterns and correlation networks than non-cancerous lung tissues. Conclusion This study provides the first insight into intratumor microbiome in BALT lymphoma using the third-generation NGS method. A distinct microbial composition suggests the presence of a unique tumor microenvironment of BALT lymphoma.

Purpose: This study analyzed the pathological complete response (pCR) rates, long-term outcomes, and biological features of human epidermal growth factor receptor 2 (HER2)-zero, HER2-low, and HER2-positive breast cancer patients undergoing neoadjuvant treatment. Methods: This single-center study included 1,667 patients who underwent neoadjuvant chemotherapy from 2008 to 2014. Patients were categorized by HER2 status, and their clinicopathological characteristics, chemotherapy responses, and recurrence-free survival (RFS) rates were analyzed. Results: Patients with HER2-low tumors were more likely to be older (p = 0.081), have a lower histological grade (p < 0.001), and have hormone receptor (HorR)-positive tumors (p < 0.001). The HER2-positive group exhibited the highest pCR rate (23.3%), followed by the HER2-zero (15.5%) and HER2-low (10.9%) groups. However, the pCR rate did not differ between HER2-low and HER2-zero tumors in the HorR-positive or HorR-negative subgroups.The 5-year RFS rates increased in the following order: HER2-low, HER2-positive, and HER2-zero (80.0%, 77.5%, and 74.5%, respectively) (log-rank test p = 0.017). A significant survival difference between patients with HER2-low and HER2-zero tumors was only identified in HorR-negative tumors (5-year RFS for HER2-low, 74.5% vs. HER2-zero, 66.0%; log-rank test p-value = 0.04). Multivariate survival analysis revealed that achieving a pCR was the most significant factor associated with improved survival (hazard ratio [HR], 4.279; p < 0.001).Compared with HER2-zero, the HRs for HER2-low and HER2-positive tumors were 0.787 (p = 0.042) and 0.728 (p = 0.005), respectively. After excluding patients who received HER2-targeted therapy, patients with HER2-low tumors exhibited better RFS than those with HER2-zero (HR 0.784, p = 0.04), whereas those with HER2-positive tumors exhibited no significant difference compared with those with HER2-low tumors (HR, 0.975; p = 0.953). Conclusion Patients with HER2-low tumors had no significant difference in pCR rate compared to HER2-zero but showed better survival, especially in HorR-negative tumors.Further investigation into biological differences is warranted.

Purpose: This study evaluated the postoperative quality of life (QoL) after various types of gastrectomy for gastric cancer. Materials and Methods: A multicenter prospective observational study was conducted in Korea using the Korean Quality of Life in Stomach Cancer Patients Study (KOQUSS)-40, a new QoL assessment tool focusing on postgastrectomy syndrome. Overall, 496 patients with gastric cancer were enrolled, and QoL was assessed at 5 time points: preoperatively and at 1, 3, 6, and 12 months after surgery. Results: Distal gastrectomy (DG) and pylorus-preserving gastrectomy (PPG) showed significantly better outcomes than total gastrectomy (TG) and proximal gastrectomy (PG) with regard to total score, indigestion, and dysphagia. DG, PPG, and TG also showed significantly better outcomes than PG in terms of dumping syndrome and worry about cancer. Postoperative QoL did not differ significantly according to anastomosis type in DG, except for Billroth I anastomosis, which achieved better bowel habit change scores than the others. No domains differed significantly when comparing double tract reconstruction and esophagogastrostomy after PG. The total QoL score correlated significantly with postoperative body weight loss (more than 10%) and extent of resection (P<0.05 for both).Reflux as assessed by KOQUSS-40 did not correlate significantly with reflux observed on gastroscopy 1 year postoperatively (P=0.064). Conclusions Our prospective observation using KOQUSS-40 revealed that DG and PPG lead to better QoL than TG and PG. Further study is needed to compare postoperative QoL according to anastomosis type in DG and PG.

Purpose: The novel curability criteria for elderly (EL) patients have been proposed to stratify their risk of lymph node metastasis (LNM), following non-curative endoscopic submucosal dissection (ESD) for early gastric cancer (EGC). Hence, this study aimed to evaluate the effectiveness of the EL criteria and compare them with those of the well-known eCura system. Materials and Methods: A retrospective analysis was performed on 143 patients who did not meet the curative ESD criteria at a tertiary hospital in Korea between 2011 and 2022. Of these, 102 underwent additional surgery, while 41 were followed up without further treatment. The LNM rates based on the EL and eCura systems were stratified and compared. Results: In the surgery group, 29.4% (30/102) patients were classified as EL-low (EL-L) and 70.2% (72/102) as EL-high (EL-H). The LNM rates (95% confidence interval) were 0.0% (0.0–11.6) and 9.7% (4.0–19.0) for EL-L and EL-H, respectively (P=0.102). EL-L was closely aligned with the eCura low-risk category, with a similar patient proportion (32.4%) and an LNM rate of 0.0% (0.0–10.6). The eCura system classified 94.1% (48/51) of the EL-L patients as lowrisk, with an 86% concordance rate (123/143). Discordant cases included patients with positive vertical margins, but without other risk factors, who were classified as EL-H without LNM. Conclusions Patients with EL-L showed no LNM, and the EL criteria demonstrated high concordance with the eCura system. The EL criteria may be as effective as the eCura system in identifying low-risk patients after non-curative ESD for EGC.