Lazertinib is an oral, third-generation, epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) for the treatment of non-small cell lung cancer (NSCLC). This case report presents a rare instance of small cell carcinoma transformation in pancreatic metastasis in a patient with EGFR-mutated NSCLC undergoing treatment with lazertinib. Small cell carcinoma transformation indicates a mechanism of treatment resistance, and tissue biopsy is essential to confirm this. When isolated progression of a lesion is suspected during TKI therapy in EGFR-mutated NSCLC, histological evaluation is necessary to confirm the transformation for the treatment strategy.

Radiofrequency ablation (RFA) is a minimally invasive treatment modality used as an alternative to surgery in patients with benign thyroid nodules, recurrent thyroid cancers (RTCs), and primary thyroid microcarcinomas. The Korean Society of Thyroid Radiology (KSThR) initially developed recommendations for the optimal use of RFA for thyroid tumors in 2009 and revised them in 2012 and 2017. As new meaningful evidence has accumulated since 2017 and in response to a growing global interest in the use of RFA for treating malignant thyroid lesions, the task force committee members of the KSThR decided to update the guidelines on the use of RFA for the management of RTCs based on a comprehensive analysis of current literature and expert consensus.

Objectives: The standard first-line treatment for Helicobacter pylori infection typically involves proton pump inhibitors, amoxicillin, and clarithromycin (PAC), yet the eradication success rates are not entirely satisfactory. Recognizing bismuth’s antibacterial properties and its potential to enhance antibiotic efficacy, this study compared the eradication success rates of a 7-day course of PAC with bismuth (PACB) versus PAC alone in patients with clarithromycin-susceptible H. pylori infections. Methods: We conducted a retrospective review at Eunpyeong St. Mary’s Hospital involving 499 patients with confirmed clarithromycin-susceptible H. pylori infection. These patients were treated either with PACB or PAC for 7 days. Clarithromycin resistance-associated point mutations were evaluated using reverse transcriptase polymerase chain reaction. Successful eradication was confirmed by a negative 13C-urea breath test. Results: Of the patients, 261 received PACB therapy, and 238 received PAC therapy. The intention-to-treat analysis showed eradication success rates of 82.8% (216/261) for PACB and 89.1% (212/238) for PAC (p=0.093). The per-protocol analysis revealed eradication rates of 85.3% (215/252) for PACB and 90.5% (210/232) for PAC (p=0.081). The incidence of adverse effects was similar between the two groups, with 41.3% (104/252) in the PACB group and 34.1% (79/232) in the PAC group (p=0.102). Conclusions Adding bismuth to the standard 7-day PAC regimen did not significantly increase eradication rates in patients with clarithromycin-susceptible H. pylori infections compared to PAC alone.

Purpose: In this study, we investigated the effect of bisphenol-A (BPA) and its major analogs, bisphenol-F (BPF), and bisphenol-S (BPS), on spermatogonial stem cells (SSCs) populations using in vitro SSC culture and in vivo transplantation models. Materials and Methods: SSCs enriched from 6- to 8-day-old C57BL/6-eGFP+ male mice testes were treated with varying concentrations of bisphenols for 7 days to examine bisphenol-derived cytotoxicity and changes in SSC characteristics. We utilized flow cytometry, immunocytochemistry, real-time quantitative reverse transcription-PCR, and western blot analysis. The functional alteration of SSCs was further investigated by examining donor SSC-derived spermatogenesis evaluation through in vivo transplantation and subsequent testis analysis. Results: BPF exhibited a similar inhibitory effect on SSCs as BPA, demonstrating a significant decrease in SSC survival, inhibition of proliferation, and induction of apoptosis. On the other hand, while BPS was comparatively weaker than BPA and BPF, it still showed significant SSC cytotoxicity. Importantly, SSCs exposed to BPA, BPF, and BPS exhibited a significant reduction in donor SSC-derived germ cell colonies per total number of cultured cells, indicating that, like BPA, BPF, and BPS can induce a comparable reduction in functional SSCs in the recipient animals. However, the progress of spermatogenesis, as evidenced by histochemistry and the expressions of PCNA and SSC specific markers, collectively indicates that BPA, BPF, and BPS may not adversely affect the spermatogenesis. Conclusions Our findings indicate that the major BPA substitutes, BPF and BPS, have significant cytotoxic effects on SSCs, similar to BPA. These effects may lead to a reduction in the functional self-renewal stem cell population and potential impacts on male fertility.

Background: Kelch-like ECH-associated protein 1 (KEAP1)–nuclear factor erythroid- 2-related factor 2 (NRF2) pathway is a major regulator protecting cells from oxidative and metabolic stress. Studies have revealed that this pathway is involved in mediating resistance to cytotoxic chemotherapy and immunotherapy; however, its implications in oncogene-addicted tumors are largely unknown. This study aimed to elucidate whether this pathway could be a potential therapeutic target for epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer. Methods: We measured the baseline expression of NRF2 using EGFR-mutant parental cells and acquired gefitinib resistant cells. We investigated whether NRF2 inhibition affected cell death in vitro and tumor growth in vivo using a xenograft mouse model, and compared the transcriptional changes before and after NRF2 inhibition. Results: Baseline NRF2 expression was enhanced in PC9 and PC9 with gefitinib resistance (PC9/GR) cells than in other cell lines, with a more prominent expression in PC9/ GR. The NRF2 inhibitor induced NRF2 downregulation and cell death in a dose-dependent manner. Cotreatment with an NRF2 inhibitor enhanced osimertinib-induced cell death in vitro, and potentiated tumor growth inhibition in a PC9/GR xenograft model. Finally, RNA sequencing revealed that NRF2 inhibition resulted in the altered expression of multiple genes involved in various signaling pathways. Conclusion We identified that NRF2 inhibition enhanced cell death and inhibited tumor growth in tyrosine kinase inhibitor (TKI)-resistant lung cancer with EGFR-mutation. Thus, NRF2 modulation may be a novel therapeutic strategy to overcome the resistance to EGFR-TKIs.

Background: This study was performed to compare the thickness of the ganglion cell-inner plexiform layer (GCIPL) depending on the presence or absence of fixation preference in patients with intermittent exotropia (IXT) with refractive values close to emmetropia and with no amblyopia. Methods: The study recruited pediatric patients diagnosed with IXT with a spherical equivalent within ±1.25 diopter and no amblyopia. The patients were categorized into two groups: a monocular exotropia group with fixation preference and an alternating exotropia group without fixation preference. GCIPL thickness was measured using spectral domain optical coherence tomography, and the macula was divided into nine sectors according to the Early Treatment Diabetic Retinopathy Study (ETDRS). GCIPL thickness in each sector was compared between the monocular and alternating exotropia groups. Results: In the monocular exotropia group, GCIPL thickness was significantly thinner in the dominant eye than in the nondominant eye in the S1 sector (91.2±7.4 μm vs. 93.3±5.2 μm, p=0.019). However, in the alternating exotropia group, there were no significant differences between the eyes across all ETDRS sectors. When comparing the interocular differences in GCIPL thickness between the two groups, the monocular exotropia group (absolute value of the dominant eye minus the nondominant eye) exhibited significantly greater differences in several ETDRS sectors than the alternating exotropia group (absolute value of the right eye minus the left eye). Conclusion The significant interocular difference in GCIPL thickness in the monocular exotropia group suggests that fixation preference may influence the anatomical structure of the macula in patients with IXT.

Background and Objectives: Outcomes of deferring percutaneous coronary intervention (PCI) without invasive physiologic assessment for intermediate coronary lesions is uncertain.We sought to compare long-term outcomes between medical treatment and PCI of intermediate lesions without invasive physiologic assessment. Methods: A total of 899 patients with intermediate coronary lesions between 50% and 70% diameter-stenosis were randomized to the conservative group (n=449) or the aggressive group (n=450). For intermediate lesions, PCI was performed in the aggressive group, but was deferred in the conservative group. The primary endpoint was major adverse cardiac events (MACE, a composite of all-cause death, myocardial infarction [MI], or ischemia-driven any revascularization) at 3 years. Results: The number of treated lesions per patient was 0.8±0.9 in the conservative group and 1.7±0.9 in the aggressive group (p=0.001). At 3 years, the conservative group had a significantly higher incidence of MACE than the aggressive group (13.8% vs. 9.3%; hazard ratio [HR], 1.49; 95% confidence interval [CI], 1.00–2.21; p=0.049), mainly driven by revascularization of target intermediate lesion (6.5% vs. 1.1%; HR, 5.69; 95% CI, 2.20–14.73;p<0.001). Between 1 and 3 years after the index procedure, compared to the aggressive group, the conservative group had significantly higher incidence of cardiac death or MI (3.2% vs.0.7%; HR, 4.34; 95% CI, 1.24–15.22; p=0.022) and ischemia-driven any revascularization. Conclusions For intermediate lesions, medical therapy alone, guided only by angiography, was associated with a higher risk of MACE at 3 years compared with performing PCI, mainly due to increased revascularization.