Purpose: While progesterone receptor (PR) negativity in luminal-type breast cancer is generally associated with worse oncologic outcomes, its prognostic role in estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-positive breast cancer remains underexplored. This study aimed to evaluate the prognostic significance of PR expression in ER-positive, HER2-positive breast cancer. Methods: A retrospective analysis was conducted on patients diagnosed with ER-positive, HER2-positive breast cancer who underwent primary surgery at Korea University Guro Hospital between January 2009 and December 2019. Patients were grouped by PR expression as negative/low (Allred score, 0–6) or strongly positive (Allred score,7 or 8). Prognostic outcomes, including disease-free survival (DFS), distant recurrence-free survival (DRFS), and breast cancer-specific survival (BCSS) were analyzed. Results: A total of 223 patients were included. Patients in the negative/low PR group were older compared to the strongly positive PR group. The negative/low PR group showed significantly worse DFS (P = 0.005) and DRFS (P = 0.014) but showed no significant difference in BCSS (P = 0.153). On multivariate analysis, negative or low PR expressions were linked to inferior DFS (hazard ratio [HR], 3.10; 95% confidence interval [CI], 1.34–7.16; P = 0.008) and DRFS (HR, 9.55; 95% CI, 1.22– 74.77; P = 0.032). Conclusion In ER-positive, HER2-positive breast cancer, negative or weak PR expression was associated with inferior DFS and DRFS compared to strong PR expression. These findings highlight the potential prognostic value of PR status in this group, underscoring its relevance in guiding treatment and follow-up strategies for more individualized patient care.

X-linked ichthyosis (XLI) is an inherited disorder of keratinization resulting from a deficiency of steroid sulfatase (STS), for which no effective therapy is currently available. E-cadherin, a key upstream regulator of keratinocyte differentiation, has been found to be markedly overexpressed in STS-deficient HaCaT cells, suggesting its potential as a therapeutic target in XLI. To investigate the functional role of E-cadherin and explore its therapeutic potential, we introduced mutations into the N-terminal region of Ecadherin and examined the resulting effects on keratinocyte differentiation. In addition, a microRNA (miR-6766) and a rationally designed gapmer antisense oligonucleotide (gASO) targeting the same E-cadherin mRNA sequence were employed to modulate E-cadherin expression in HaCaT cells. Mutations within the N-terminal region of E-cadherin significantly reduced keratin 1 expression, underscoring the critical role of this domain in regulating keratinocyte differentiation. Treatment with miR-6766 led todownregulation of both early and terminal differentiation markers. Building on this, the gASO modified with 2′-O-methoxyethyl andphosphorothioate linkages exhibited enhanced potency and stability, resulting in stronger suppression of E-cadherin and keratin 1 expression compared with miR-6766 (maintained 37.7% greater inhibition of E-cadherin at 96 h and 35.7% greater inhibition of keratin 1 at 96 h). Furthermore, gASO treatment induced a concentration-dependent reduction in early (keratin 1 and keratin 10) and terminal (transglutaminase 1, involucrin, and loricrin) differentiation markers. These findings demonstrate that an E-cadherin– targeting gASO effectively suppresses abnormal keratinocyte differentiation and may serve as a promising therapeutic strategy for X-linked ichthyosis.

Human breast milk (HBM) is an ideal nutritional source for the growth and development of infants. In addition, HBM contains hormones, growth factors, microRNAs and exosomes that perform various physiological functions. This study investigates the immunomodulatory effects of HBM-derived exosomes on myeloid cells and chondrocytes, and implications for juvenile idiopathic arthritis. HBM-derived exosomes were isolated and characterized using nanoparticle track analyzer and Western blotting. The HBM-derived exosomes treatment decreased the expression of inflammatory mediators and proinflammatory cytokines in mouse peritoneal macrophages upon lipopolysaccharide stimulation. Flow cytometry analysis of bone marrow-derived macrophages indicated that exosomes promoted M2 polarization, as evidenced by a decrease in cells expressing CD80 (M1 marker) and a concurrent increase in cells expressing M2 marker CD206. In addition, exosome treatment attenuated the mitogen-activated protein kinase signaling pathway by reducing the phosphorylation of extracellular signal-regulated kinase, c-Jun N-terminal kinase, p38 mitogen-activated protein kinase, and IκB-α, thereby reducing the expression of inducible nitric oxide synthase, cyclooxygenase-2, metalloprotease (MMP)-1, MMP-3, and MMP-13 in SW1353 chondrocytes following IL-1β stimulation. These findings suggest that HBM-derived exosomes promote macrophage polarization toward an anti-inflammatory M2 phenotype and exert significant immunomodulatory effects.

Purpose: Limited treatment options exist for patients with metastatic castration-resistant prostate cancer (mCRPC) after the failure of taxane-based chemotherapy and novel hormonal therapy. Here, we report the safety and efficacy of ifosfamide and mesna in patients with mCRPC after the failure of taxane-based chemotherapy and novel hormonal therapy (NCT06236789). Materials and Methods: Patients with histologically confirmed prostate cancer who had failed taxane-based chemotherapy and novel hormonal therapy received ifosfamide 2,500 mg/m2 and mesna 1,500 mg/m2 on days 1–3, repeated every 21 days. Safety, objective response rate, disease control rate, reduction in serum prostate-specific antigen (PSA) concentration by >50% (PSA50) or >90% (PSA90), radiographic progression-free survival (rPFS), and overall survival (OS) were analyzed. Results: A total of 47 patients with mCRPC were included in the study. The median number of lines of treatment was 5 (range, 3 to 7). All patients were previously administered docetaxel and novel hormonal therapies including abiraterone (51.1%) and/or enzalutamide (61.7%). Thirty-eight patients (80.9%) were administered cabazitaxel. The objective response and disease control rates were 21.3% and 80.9%, respectively. PSA50 and PSA90 were achieved in 31.9% and 10.6%, respectively. During a median follow-up duration of 54.3 months, rPFS and OS were 5.0 and 9.0 months, respectively. All the patients experienced treatment-related adverse events of any grades; however, no new safety signs were detected. Genomic biomarker analysis revealed that alterations in the TP53 pathway were associated with inferior rPFS and OS. Conclusion Ifosfamide and mesna showed appreciable efficacy and manageable safety profiles in heavily treated patients with mCRPC.

Purpose: Current guidelines recommend vaccination at least 2 weeks before chemotherapy initiation to optimize the immune response despite limited evidence. Our previous study indicated no differences in short-term immune response for the 13-valent pneumococcal conjugate vaccine (PCV13) according to the vaccination timing. This study aims to investigate the long-term efficacy of PCV13 and clinical factors associated with the respective antibody response. Materials and Methods: Patients with gastric or colorectal cancer who received adjuvant chemotherapy were enrolled and divided into two groups: vaccinated 2 weeks before chemotherapy (arm A) and vaccinated concurrently with chemotherapy (arm B). Serum samples were collected before vaccination and in one month, 3 years, and 5 years. Immune responses were measured using enzyme-linked immunosorbent assay and multiplex opsonophagocytosis assay. Results: Including 63 patients, both groups showed an initial increase in the geometric mean titers of opsonophagocytic activity and the geometric mean concentrations of serotype-specific IgG levels after one month, followed by a decline at 3 and 5 years, particularly for serotypes 1, 14, 18C, and 19A. Despite the decline, global protection was maintained for 5 years, although global response decreased. The two arms did not show significant differences in immunogenicity nor in factors such as vaccination timing, age, cancer type, or chemotherapy regimen. Conclusion Vaccination timing is not a significant factor for the immunogenicity of PCV13 in cancer patients undergoing adjuvant chemotherapy. Global protection against pneumococcal infection was sustained for > 5 years, and global response remained in over half of patients.

Purpose: Although human epidermal growth factor receptor 2 (HER2) positivity is prevalent in microinvasive breast cancer (MIBC), data focused on HER2-positive MIBC are limited. We investigated the clinical course and long-term outcomes of HER2-positive MIBC and evaluated the role of adjuvant chemotherapy. Materials and Methods: The study included patients with curatively resected pT1mi pN0 HER2-positive breast cancer between January 2000 and January 2020. Treatments and survival outcomes, including invasive breast cancer-free survival (IBCFS), distant recurrence-free survival (DRFS), and overall survival (OS) were analyzed. Results: The analysis included 799 female patients. The median age was 51 years (range, 23 to 79 years), and 51.6% (n=412) were premenopausal. Multifocality was confirmed in 17.3% (n=138), and estrogen receptor (ER) positivity in 29.8% (n=238). Adjuvant chemotherapy was administered to 17.5% (n=140), with doxifluridine in 96.4% of cases. One patient (0.1%) received trastuzumab. With a median follow-up of 119.0 months (95% confidence interval [CI], 114.0 to 127.0), the 8-year IBCFS, DRFS, and OS were 91.2% (95% CI, 89.1 to 93.3), 97.5% (95% CI, 96.4 to 98.7), and 98.8% (95% CI, 98.0 to 99.6), respectively. No significant differences were observed between patients with and without adjuvant chemotherapy. The lack of differences in IBCFS by chemotherapy was consistent across subgroups, including pre-/postmenopausal patients, grade 1-2/3 tumors, and ER-negative disease. Conclusion A clinically meaningful proportion of HER2-positive MIBC patients experience IBCFS events with long-term follow-up. Adjuvant chemotherapy did not improve survival, potentially due to the use of an outdated, ineffective regimen. The role of modern adjuvant regimens, particularly those incorporating HER2-targeted therapy, warrants further exploration.

Objectives: . Differentiated thyroid cancer (DTC) has a favorable prognosis. However, indeterminate lymph nodes (LNs) are common, making it challenging to distinguish recurrent from persistent DTC. Previous studies have not specifically compared the prognosis between recurrent and persistent DTC. Therefore, we aimed to compare prognosis and oncologic characteristics between these two groups. Methods: . This retrospective cohort study was conducted at a single tertiary care institution and included 265 patients with DTC (recurrent, 109; persistent, 156) who underwent reoperation between November 1, 1999, and August 31, 2018, for structural disease. Patients with distant metastasis at the time of initial diagnosis were excluded. Clinical and oncological characteristics, patterns of LN metastasis, disease-free survival (DFS), and overall survival (OS) were compared between the two groups. For DFS, time zero was defined as the date of the second operation. Results: . Recurrent DTC had a higher incidence of central LN metastasis (P=0.003), infield recurrence (P<0.001), and distant metastasis (P<0.001). In contrast, persistent DTC more frequently exhibited lateral LN metastasis (P=0.003) and outfield recurrence (P<0.001). The most common site of neck LN metastasis was ipsilateral level VI/VII (51.4%) in recurrent DTC and ipsilateral level IV (43.0%) in persistent DTC. Ten-year DFS was significantly lower in recurrent DTC than in persistent DTC (41.0% vs. 67.9%; P<0.001). Recurrent DTC, older age, a higher number of metastatic LNs at the second operation (first reoperation), and R1/R2 resection at the second operation were associated with decreased DFS. OS did not significantly differ between recurrent and persistent DTC (P=0.160). Conclusion . Recurrent DTC is associated with poorer DFS than persistent DTC, although OS does not significantly differ between the two groups.

Background: Carbon suspension with laser irradiation was used for facial melasma, but it produces harmful fumes. Gold and diamond are biocompatible and chemically inert, and expected to act as potent chromophores and microdermabrasion agents, respectively. Objective: This study aimed to evaluate the efficacy and safety of microgold and microdiamond suspensions with a 1,064 nm picosecond neodymium-doped yttrium aluminum garnet (Nd:YAG) laser for melasma. Methods: Ten Korean patients received 2 laser sessions using gold and diamond suspension at 2-week intervals. Melasma area severity index (MASI), melanin index (MI), erythema index (EI), Physician/Subject global aesthetic improvement scale (PGAIS/SGAIS), and adverse events were assessed at baseline, week 2 and week 4. Results: MASI and MI scores significantly improved. EI score showed no significant changes.All patients showed aesthetic improvement by PGAIS and SGAIS. No severe or unexpected adverse events were reported. Conclusion The topical microgold and microdiamond suspension combined with a 1,064 nm picosecond Nd:YAG laser appears to be a safe and effective treatment option for facial melasma.

Purpose: Esophagojejunal anastomotic leakage (EJAL) represents a severe postoperative complication following total or proximal gastrectomy. Treatment strategies include conservative management, endoscopic interventions, and surgery; however, comparative data remain limited. This study aimed to compare clinical outcomes of different strategies to identify the optimal approach based on anastomotic defect size. Materials and Methods: This retrospective study reviewed 100 patients diagnosed with EJAL between January 2015 and October 2024. Patients were categorized into four groups:conservative management, endoscopic vacuum-assisted closure (E-VAC), other endoscopic treatments, and surgery. The primary outcomes were leakage duration and length of hospital stay after EJAL diagnosis, whereas the secondary outcome was time to C-reactive protein normalization. Subgroup analyses were performed according to defect size. Results: Among the 100 patients, 76 were male and 24 were female, with a mean age of 65.7 years. Conservative treatment was the most common modality (53%), followed by other endoscopic treatments (19%), E-VAC (14%), and surgery (14%). In patients with a defect size <1 cm, conservative treatment was associated with significantly shorter leakage duration (P=0.035) and earlier resumption of diet (P=0.029) compared with endoscopic treatment.Among those with defects ≥2 cm, E-VAC demonstrated the most favorable median outcomes across all variables; however, statistical significance was not achieved because of the small sample size. Conclusions Conservative treatment appears to be the most effective treatment strategy for EJAL with anastomotic defects <1 cm. For larger defects (≥2 cm), E-VAC may offer clinical benefit, although further studies are needed to confirm its efficacy. These findings highlight the importance of individualized treatment selection based on defect size.

Purpose: This study explored the experiences of physicians and nurses providing end-oflife care in Korean acute care hospitals. It aimed to identify the challenges faced in caring for dying patients and to suggest strategies for improving hospital-based end-of-life care. Methods: A qualitative exploratory design was employed using focus group interviews.Eleven healthcare professionals (five physicians and six nurses) working in tertiary or general hospitals participated in the study between July and August 2018. The interviews were conducted using a semi-structured guide covering seven thematic areas. All sessions were audio-recorded, transcribed verbatim, and analyzed thematically following Braun and Clarke’s framework. Results: Six major themes emerged: (1) communication with patients and families, (2) physical care for dying patients, (3) psychological and spiritual support, (4) hospital environment and system constraints, (5) moral distress and emotional burden on healthcare providers, and (6) suggestions for improvement. The participants described difficulties in open communication, limited resources for comfort care, emotional strain from invasive treatment at the end of life, and the absence of standardized institutional protocols.They emphasized the need for structured communication training, multidisciplinary collaboration, and integration of palliative care principles into acute care practice. Conclusion Physicians and nurses play a pivotal yet emotionally demanding role in providing end-oflife care in acute hospitals. Institutional reforms, including education, protocol development, and supportive environments, are essential to ensuring dignified, patient-centered care and sustain healthcare providers in their professional roles.