Background: As nationwide government-led whole-genome sequencing (WGS) projects progress, optimizing the clinical integration of large-scale WGS results is crucial. We explored how the initial analysis from Korea’s First WGS Pilot Study for Rare Diseases was applied in clinical practice, and then we reanalyzed the data comprehensively at Samsung Medical Center (SMC) Seoul, Korea. Methods: A prospective cohort study designed to collect WGS data under a Korean national initiative was conducted from August 2020 to December 2021. We focused on patients with rare diseases recruited from 16 university hospitals. The participants included 5,000 individuals (2,200 probands and 2,800 family members). The initial WGS data and diagnostic reference reports (from 682 probands and 484 family members), generated based on the First Korean WGS Pilot Study for Rare Diseases, were subsequently reanalyzed by SMC. Results: The initial analysis of the First Korean WGS Pilot Study data revealed a diagnostic rate of 17%. Upon receiving these results, the SMC conducted two rounds of reanalysis, increasing the diagnostic rate from 15% in the first analysis, to 18% in the second, and finally to 24% in the third (P = 1.6 × 10 −5 ). Key factors in improving the genetic diagnosis included increased detection of novel (likely) pathogenic variants (P = 1.0 × 10 −4 ), improved diagnostic rates with larger family recruitment (P = 0.004), and refined clinical information for more precise genotype–phenotype correlation analysis (40%). Conclusions Although national WGS projects lay a foundation for rare disease diagnosis, hospital-level reanalysis and multidisciplinary collaborations are crucial for optimizing diagnostic outcomes.

Purpose: Radical cystectomy (RC) is associated with substantial postoperative morbidity, and unplanned readmission remains common despite advances in perioperative management. However, the association between postoperative readmission due to complications and oncologic outcomes after RC for bladder cancer has not been clearly defined. We evaluated the impact of postoperative readmission on overall survival (OS) and cancer-specific survival (CSS) after RC for bladder cancer. Materials and Methods: We retrospectively analyzed 3,972 patients who underwent RC for bladder cancer in a multicenter cohort. Postoperative readmission was defined as unplanned hospitalization within 90 days postsurgery due to surgery-related complications. Survival outcomes were assessed using the Kaplan-Meier method and compared using the log-rank test. Univariable and multivariable Cox proportional hazards regression analyses were performed to identify independent predictors of OS and CSS. Results: Among the study population, 916 patients (23.1%) experienced postoperative readmission. Baseline and perioperative characteristics were generally comparable between patients with and without readmission. Kaplan-Meier analyses demonstrated significantly worse OS and CSS among patients who experienced postoperative readmission (both log-rank p<0.001). In multivariable analyses adjusting for clinicopathological factors, postoperative readmission remained independently associated with worse OS (hazard ratio [HR], 1.654; 95% confidence interval [CI], 1.464–1.868; p<0.001) and CSS (HR, 1.761; 95% CI, 1.509–2.055; p<0.001). Conclusion Postoperative readmission within 90 days after RC was independently associated with inferior long-term oncologic outcomes. These findings suggest the importance of strategies aimed at preventing postoperative complications and subsequent readmission.

Background: Citrin deficiency is an autosomal recessive disorder caused by pathogenic variants in SLC25A13, presenting with various age-dependent clinical phenotypes and a broad spectrum of severity. However, few studies have examined the frequency and prevalence of citrin deficiency. We aimed to analyze the carrier frequency and disease prevalence in East Asian populations and Koreans. Methods: We comprehensively reviewed the literature and conducted a cross-sectional study to analyze genomic databases, including the Genome Aggregation Database (gnomAD), Korean Variant Archive (KOVA), and Tohoku Medical Megabank Organization (ToMMo), to identify pathogenic SLC25A13 variants in East Asian populations. A founder 3-kilobase (kb) insertion in intron 16 of SLC25A13 was investigated using whole-genome sequencing data from 681 Koreans with the Linux grep command. Results: Twenty-three pathogenic SLC25A13 variants were identified, with c.852_855del being the most common. Analysis of data from 17,501 East Asian individuals in the gnomAD and ToMMo databases revealed a carrier frequency of 1 in 62 people. Analysis of data from 7,214 individuals in the gnomAD and KOVA databases revealed a carrier frequency of 1 in 86, corresponding to an estimated disease prevalence of 1 in 29,502.c.1177+1G > A was identified as the most prevalent pathogenic variant in Koreans. The 3 kb insertion in intron 16 was detected in three out of 681 individuals, indicating a carrier frequency of 1 in 228. Conclusions The high carrier frequency of citrin deficiency in East Asians highlights the need for enhanced genetic screening and counseling, particularly in Korea, providing a valuable reference for future studies on genetic diversity and pathogenic variants in this population.

Purpose: This study aims to evaluate the treatment approaches and locoregional patterns for adenoid cystic carcinoma (ACC) in the breast, which is an uncommon malignant tumor with limited clinical data. Materials and Methods: A total of 93 patients diagnosed with primary ACC in the breast between 1992 and 2022 were collected from multi-institutions. All patients underwent surgical resection, including breast-conserving surgery (BCS) or total mastectomy (TM). Recurrence patterns and locoregional recurrence-free survival (LRFS) were assessed. Results: Seventy-five patients (80.7%) underwent BCS, and 71 of them (94.7%) received post-operative radiation therapy (PORT). Eighteen patients (19.3%) underwent TM, with five of them (27.8%) also receiving PORT. With a median follow-up of 50 months, the LRFS rate was 84.2% at 5 years. Local recurrence (LR) was observed in five patients (5.4%) and four cases (80%) of the LR occurred in the tumor bed. Three of LR (3/75, 4.0%) had a history of BCS and PORT, meanwhile, two of LR (2/18, 11.1%) had a history of mastectomy. Regional recurrence occurred in two patients (2.2%), and both cases had a history of PORT with (n=1) and without (n=1) irradiation of the regional lymph nodes. Partial breast irradiation (p=0.35), BCS (p=0.96) and PORT in BCS group (p=0.33) had no significant association with LRFS. Conclusion BCS followed by PORT was the predominant treatment approach for ACC of the breast and LR mostly occurred in the tumor bed. The findings of this study suggest that partial breast irradiation might be considered for PORT in primary breast ACC.

Purpose: This study aims to evaluate the treatment approaches and locoregional patterns for adenoid cystic carcinoma (ACC) in the breast, which is an uncommon malignant tumor with limited clinical data. Materials and Methods: A total of 93 patients diagnosed with primary ACC in the breast between 1992 and 2022 were collected from multi-institutions. All patients underwent surgical resection, including breast-conserving surgery (BCS) or total mastectomy (TM). Recurrence patterns and locoregional recurrence-free survival (LRFS) were assessed. Results: Seventy-five patients (80.7%) underwent BCS, and 71 of them (94.7%) received post-operative radiation therapy (PORT). Eighteen patients (19.3%) underwent TM, with five of them (27.8%) also receiving PORT. With a median follow-up of 50 months, the LRFS rate was 84.2% at 5 years. Local recurrence (LR) was observed in five patients (5.4%) and four cases (80%) of the LR occurred in the tumor bed. Three of LR (3/75, 4.0%) had a history of BCS and PORT, meanwhile, two of LR (2/18, 11.1%) had a history of mastectomy. Regional recurrence occurred in two patients (2.2%), and both cases had a history of PORT with (n=1) and without (n=1) irradiation of the regional lymph nodes. Partial breast irradiation (p=0.35), BCS (p=0.96) and PORT in BCS group (p=0.33) had no significant association with LRFS. Conclusion BCS followed by PORT was the predominant treatment approach for ACC of the breast and LR mostly occurred in the tumor bed. The findings of this study suggest that partial breast irradiation might be considered for PORT in primary breast ACC.

Purpose: This study aims to evaluate the treatment approaches and locoregional patterns for adenoid cystic carcinoma (ACC) in the breast, which is an uncommon malignant tumor with limited clinical data. Materials and Methods: A total of 93 patients diagnosed with primary ACC in the breast between 1992 and 2022 were collected from multi-institutions. All patients underwent surgical resection, including breast-conserving surgery (BCS) or total mastectomy (TM). Recurrence patterns and locoregional recurrence-free survival (LRFS) were assessed. Results: Seventy-five patients (80.7%) underwent BCS, and 71 of them (94.7%) received post-operative radiation therapy (PORT). Eighteen patients (19.3%) underwent TM, with five of them (27.8%) also receiving PORT. With a median follow-up of 50 months, the LRFS rate was 84.2% at 5 years. Local recurrence (LR) was observed in five patients (5.4%) and four cases (80%) of the LR occurred in the tumor bed. Three of LR (3/75, 4.0%) had a history of BCS and PORT, meanwhile, two of LR (2/18, 11.1%) had a history of mastectomy. Regional recurrence occurred in two patients (2.2%), and both cases had a history of PORT with (n=1) and without (n=1) irradiation of the regional lymph nodes. Partial breast irradiation (p=0.35), BCS (p=0.96) and PORT in BCS group (p=0.33) had no significant association with LRFS. Conclusion BCS followed by PORT was the predominant treatment approach for ACC of the breast and LR mostly occurred in the tumor bed. The findings of this study suggest that partial breast irradiation might be considered for PORT in primary breast ACC.

Purpose: Although bladder cancer occurs three to 4 times more frequently in men than in women, the relative number of deaths compared to incidence is higher in women, suggesting that women have a worse prognosis than men. Emerging evidence indicates that the activity of the sex steroid hormone pathway may play a role in bladder cancer development, with demonstrations that both androgens and estrogens have biological effects on bladder cancer in vitro and in vivo. This study investigates the influence of sex and menopausal status on recurrence and cancer-specific death (CSD) in bladder cancer patients undergoing radical cystectomy (RC). Materials and Methods: This retrospective analysis included 3,913 patients from the Korean Bladder Cancer Study Group Database who underwent RC between 2010 and 2019. Patients were categorized based on gender and menopausal status (≤50 years: premenopausal; >50 years: postmenopausal). Pathological factors, neoadjuvant chemotherapy, recurrence, and CSD rates were analyzed using chi-square and Fisher exact tests. Results: Among the 3,913 patients, 400 (10.2%) were female. Premenopausal females exhibited significantly lower recurrence rates (28.6%) compared to postmenopausal females (45.7%). CSD rates were similarly reduced in premenopausal females (12.0% vs. 22.2% in postmenopausal females). No significant sex differences in recurrence or CSD were observed among premenopausal patients. Pathological T stage, nodal status, and lymphovascular invasion were significantly associated with recurrence in males, while nodal status alone was significant in females. Neoadjuvant chemotherapy was significantly more frequently administered to male patients under the age of 50, while no difference was observed in the administration of neoadjuvant chemotherapy among female patients based on menopausal status. Conclusion Hormonal changes associated with menopause significantly influence bladder cancer outcomes in women. Premenopausal hormonal environments seem protective, underscoring the need for further research into hormone-driven mechanisms in bladder cancer.

Purpose: This study aimed to evaluate the prognostic value of a trifecta, defined as negative soft tissue surgical margin (STSM), removal of ≥16 lymph nodes, and absence of major complications (Clavien-Dindo classification grade >III) within 90 days, after radical cystectomy (RC), using a large multicenter cohort. Materials and Methods: We retrospectively analyzed data from 3,972 patients with bladder cancer who underwent RC at 11 tertiary centers in South Korea between 2003 and 2024. Survival outcomes, including overall survival (OS), cancer-specific survival (CSS), and recurrence-free survival (RFS), were compared according to trifecta status using Kaplan-Meier and Cox regression analyses. Propensity score matching was performed to adjust for baseline differences. Results: A total of 2,014 eligible patients were included in the final analysis, and the trifecta was achieved in 47.8%. Kaplan-Meier analysis demonstrated significantly improved 5- and 10-year OS (66.7% vs. 62.0%; 62.9% vs. 57.2%; p=0.002), CSS (79.3% vs. 75.4%; 77.8% vs. 73.8%; p=0.008), and RFS (62.7% vs. 57.6%; 60.8% vs. 55.2%; p=0.001) in the trifecta group. In multivariable analysis, trifecta achievement was significantly associated with better OS (HR, 0.813; p=0.008), CSS (HR, 0.787; p=0.017), and RFS (HR, 0.844; p=0.036). Among individual components, negative STSM showed the strongest prognostic effect across all endpoints. Conclusions In this large multicenter study, patients who achieved the RC trifecta exhibited significantly superior survival outcomes compared with those who did not. The trifecta may serve as a practical and standardized metric for assessing surgical quality and performance in RC. Future prospective studies are warranted to validate its prognostic and quality-assurance utility.

Endoplasmic reticulum (ER) stress plays a crucial role in liver diseases, affecting various types of hepatic cells. While studies have focused on the link between ER stress and hepatocytes as well as hepatic stellate cells (HSCs), the precise involvement of hepatic macrophages in ER stress-induced liver injury remains poorly understood. Here, we examined the effects of ER stress on hepatic macrophages and their role in liver injury. Acute ER stress led to the accumulation and activation of hepatic macrophages, which preceded hepatocyte apoptosis. Notably, macrophage depletion mitigated liver injury induced by ER stress, underscoring their detrimental role. Mechanistic studies revealed that ER stress stimulates macrophages predominantly via the PERK signaling pathway, regardless of its canonical substrate ATF4. hnRNPA1 has been identified as a crucial mediator of PERK-driven macrophage activation, as the overexpression of hnRNPA1 effectively reduced ER stress and suppressed pro-inflammatory activation. We observed that hnRNPA1 interacts with mRNAs that encode UPR-related proteins, indicating its role in the regulation of ER stress response in macrophages. These findings illuminate the cell type-specific responses to ER stress and the significance of hepatic macrophages in ER stress-induced liver injury. Collectively, the PERK-hnRNPA1 axis has been discovered as a molecular mechanism for macrophage activation, presenting prospective therapeutic targets for inflammatory hepatic diseases such as acute liver injury.

Purpose: The purpose of this study was to explore and assess the experiences of cancer patients and their caregivers who had been admitted to comprehensive nursing care service wards. Methods: Data were collected from 10 patients and 10 caregivers by in-depth interviews. The data were analyzed using content analysis of Downe-Wamboldt. Results: Three categories and seven subcategories were extracted. 1) Realizing institutional limitations of comprehensive nursing care service: ‘Wishing for precise operating systems based on patient severity,’ ‘Anticipating active caregiver participation in treatment process,’ ‘Requiring a countermeasure for safety accidents,’ 2) Professional nursing service which provides relief: ‘Patient-centered professional nursing service,’ ‘Inpatient service that provides relief for patients and caregivers,’ 3) Anticipating continuous use of the service: ‘Inpatient service which users are willing to reuse,’ ‘Wishing for expansion and reinforcement of the service.’ Conclusion Cancer patients and their caregivers experienced institutional limitations while satisfied with professional nursing service and willing to reuse the service. To improve this situation, institutional support such as separate wards for severe patients, measures for active caregiver participation and prevention of safety accidents, and adequate staffing would be helpful for relatively severe level cancer patients and their caregivers.