Purpose: Triple-negative breast cancer (TNBC) is a frequent phenotype of BRCA-mutanttumors. Tumors with BRCAness may show characteristics of BRCA-mutant tumors and respond to similar treatments. Next-generation sequencing is an efficient and cost-effective method for simultaneously sequencing multiple cancer susceptibility genes, surpassing conventional Sanger testing. Methods: A total of 148 women with TNBC were recruited from December 2015 to November 2018, as part of a sub-analysis based on the PEARLY trial data. Of them, 103 patients received neoadjuvant chemotherapy (NCT). The targeted genes related to hereditary cancers were sequenced using the 65-gene germline next-generation sequencing (gNGS) panel pathogenic and likely pathogenic variants (P&LPs) were determined by Sanger sequencing. We examined the occurrence of pathologic complete remission (ypCR) in patients with P&LPs. Results: The patients’ median age was 47 years (range, 27–69 years). Twenty (13.7%) of 148 patients had P&LP in six genes, including BARD1 (n = 2), BRCA1 (n = 9), BRCA2 (n = 5), CHEK2 (n = 1), RAD51C (n = 1), and RAD51D (n = 2). Among the 103 patients with NCT, 43 (41.7%) achieved ypCR (P&LPs; 9 individuals vs. non-variants; 34 individuals). Among the 103 patients with NCT, 14 (9.3%) had P&LPs. Nine of 14 patients with P&LPs, including BARD1 (n = 2), BRCA1 (n = 4), BRCA2 (n = 1), RAD51C (n = 1), and RAD51D (n = 1), achieved ypCR, showing a trend toward statistical significance (p = 0.066). Conclusion Germline P&LP mutations in TNBC patients can be detected by gNGS. This panel test can identify BRCA and BRCAness mutations that may predict ypCR in TNBC.

Purpose: Axillary surgery is increasingly omitted in patients with early-stage breast cancer undergoing upfront surgery, as supported by trials such as SOUND and INSEMA. However, in the neoadjuvant setting, the omission of axillary surgery has only been explored in small single-arm studies involving highly selected patients with confirmed breast pathologic complete response (pCR). The NeoNAUTILUS trial aimed to evaluate the oncologic safety of omitting sentinel lymph node biopsy (SLNB) in patients with a high probability of achieving an axillary pCR (ypN0) following neoadjuvant systemic therapy (NST), regardless of breast pCR status. Methods NeoNAUTILUS is a prospective, multicenter, randomized, controlled, noninferiority trial conducted at 12 tertiary centers in Korea. Eligible participants were women with clinical T1–T3, N0, or selected N1 invasive breast cancer, who completed NST and were candidates for breast-conserving surgery (BCS). Prior to enrollment, all patients underwent axillary ultrasound after NST completion to exclude suspicious lymph nodes. Patients with clinical N0 disease of any subtype were eligible for inclusion. Patients with clinical N1 disease with human epidermal growth factor receptor 2-positive or triple-negative tumors may be included if their primary tumor demonstrates a > 30% reduction on magnetic resonance imaging after NST. Participants were randomized 1:1 to undergo BCS with or without SLNB, stratified by clinical nodal status and tumor subtype. Patients were randomized and remained blinded until surgery. The primary endpoint is the 5-year invasive disease-free survival. A total of 464 patients are expected to be enrolled over 3 years, with a 5-year follow-up period.Discussion: NeoNAUTILUS is the first randomized trial to assess the omission of axillary surgery after NST based on the predicted nodal response, independent of breast pCR. This study may redefine axillary management in the neoadjuvant setting by identifying patients who can safely avoid SLNB, thereby reducing surgical morbidity without compromising oncologic outcomes.

Purpose: Triple-negative breast cancer (TNBC) is a heterogeneous and aggressive subtype of breast cancer associated with poor clinical outcomes. Although programmed death ligand 1 (PD-L1) expression has emerged as both a prognostic and predictive biomarker, its utility remains limited, especially in PD-L1-negative tumors. The identification of additional molecular markers is crucial for improving prognostic stratification and guiding treatment strategies. Methods: Formalin-fixed, paraffin-embedded tumor tissues from 38 patients with TNBC were analyzed. PD-L1 expression was assessed using immunohistochemistry and categorized as positive or negative. Whole-exome sequencing was performed, and somatic variants were analyzed using Maftools. Mutational signatures were compared with the Catalogue Of Somatic Mutations In Cancer reference profiles. Survival analyses were performed to evaluate the prognostic significance of the identified variants. Results: Mutational landscape analysis revealed that C>T and G>A transitions were the most frequent base substitutions. PD-L1-negative tumors exhibited a predominance of single-base substitution (SBS) 5, whereas PD-L1-positive tumors resembled SBS6, reflecting potential differences in the underlying mutational processes. Comparative analysis identified 12 PD-L1-negative-specific and seven PD-L1-positive-specific variants. Among PD-L1-negative tumors, mutations in ANGPTL5 and KIAA1549L were significantly associated with worse overall survival. Conclusion Our findings highlight distinct mutational profiles and prognostic variants according to PD-L1 status in TNBC. ANGPTL5 and KIAA1549L variants may serve as potential prognostic markers for PD-L1-negative tumors. These results underscore the value of incorporating genomic information to refine the prognostic stratification of TNBC.

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: Nutritional support for adult critically ill patients is essential due to the high risk of malnutrition, which can lead to severe complications. This paper aims to develop evidence-based guidelines to optimize nutritional support in intensive care units (ICUs). Methods: The Grading Recommendations, Assessment, Development and Evaluation process was used to develop and summarize the evidence on which the recommendations were based. Clinical outcomes were assessed for seven key questions. Results: We recommend the following: (1) initiate enteral nutrition (EN) within 48 hours after treatment as it is associated with improved outcomes, including reduced infection rates and shorter ICU stays; (2) early EN is preferred over early parenteral nutrition due to better clinical outcomes; (3) the use of supplementary parenteral nutrition to meet energy targets during the first week of ICU admission in patients receiving early EN is conditionally recommended based on patient-specific needs; (4) limited caloric support should be supplied to prevent overfeeding and related complications, particularly in the early phase of critical illness; (5) higher protein intake is suggested to improve clinical outcomes, such as muscle preservation and overall recovery; (6) additional enteral or parenteral glutamine is conditionally recommended against due to the lack of significant benefit and potential harm; and (7) fish oil-containing lipid emulsions is conditionally recommended due to their potential to enhance clinical outcomes, including reduced infection rates and shorter ICU stays. Conclusion These evidence-based recommendations can improve clinical outcomes and support healthcare providers in making informed decisions about nutritional interventions in the ICU.

Purpose: Nutritional support for adult critically ill patients is essential due to the high risk of malnutrition, which can lead to severe complications. This paper aims to develop evidence-based guidelines to optimize nutritional support in intensive care units (ICUs). Methods: The Grading Recommendations, Assessment, Development and Evaluation process was used to develop and summarize the evidence on which the recommendations were based. Clinical outcomes were assessed for seven key questions. Results: We recommend the following: (1) initiate enteral nutrition (EN) within 48 hours after treatment as it is associated with improved outcomes, including reduced infection rates and shorter ICU stays; (2) early EN is preferred over early parenteral nutrition due to better clinical outcomes; (3) the use of supplementary parenteral nutrition to meet energy targets during the first week of ICU admission in patients receiving early EN is conditionally recommended based on patient-specific needs; (4) limited caloric support should be supplied to prevent overfeeding and related complications, particularly in the early phase of critical illness; (5) higher protein intake is suggested to improve clinical outcomes, such as muscle preservation and overall recovery; (6) additional enteral or parenteral glutamine is conditionally recommended against due to the lack of significant benefit and potential harm; and (7) fish oil-containing lipid emulsions is conditionally recommended due to their potential to enhance clinical outcomes, including reduced infection rates and shorter ICU stays. Conclusion These evidence-based recommendations can improve clinical outcomes and support healthcare providers in making informed decisions about nutritional interventions in the ICU.

Purpose: Nutritional support for adult critically ill patients is essential due to the high risk of malnutrition, which can lead to severe complications. This paper aims to develop evidence-based guidelines to optimize nutritional support in intensive care units (ICUs). Methods: The Grading Recommendations, Assessment, Development and Evaluation process was used to develop and summarize the evidence on which the recommendations were based. Clinical outcomes were assessed for seven key questions. Results: We recommend the following: (1) initiate enteral nutrition (EN) within 48 hours after treatment as it is associated with improved outcomes, including reduced infection rates and shorter ICU stays; (2) early EN is preferred over early parenteral nutrition due to better clinical outcomes; (3) the use of supplementary parenteral nutrition to meet energy targets during the first week of ICU admission in patients receiving early EN is conditionally recommended based on patient-specific needs; (4) limited caloric support should be supplied to prevent overfeeding and related complications, particularly in the early phase of critical illness; (5) higher protein intake is suggested to improve clinical outcomes, such as muscle preservation and overall recovery; (6) additional enteral or parenteral glutamine is conditionally recommended against due to the lack of significant benefit and potential harm; and (7) fish oil-containing lipid emulsions is conditionally recommended due to their potential to enhance clinical outcomes, including reduced infection rates and shorter ICU stays. Conclusion These evidence-based recommendations can improve clinical outcomes and support healthcare providers in making informed decisions about nutritional interventions in the ICU.

Differentiated thyroid cancer demonstrates a wide range of clinical presentations, from very indolent cases to those with an aggressive prognosis. Therefore, diagnosing and treating each cancer appropriately based on its risk status is important. The Korean Thyroid Association (KTA) has provided and amended the clinical guidelines for thyroid cancer management since 2007. The main changes in this revised 2024 guideline include 1) individualization of surgical extent according to pathological tests and clinical findings, 2) application of active surveillance in low-risk papillary thyroid microcarcinoma, 3) indications for minimally invasive surgery, 4) adoption of World Health Organization pathological diagnostic criteria and definition of terminology in Korean, 5) update on literature evidence of recurrence risk for initial risk stratification, 6) addition of the role of molecular testing, 7) addition of definition of initial risk stratification and targeting thyroid stimulating hormone (TSH) concentrations according to ongoing risk stratification (ORS), 8) addition of treatment of perioperative hypoparathyroidism, 9) update on systemic chemotherapy, and 10) addition of treatment for pediatric patients with thyroid cancer.

The primary objective of initial treatment for thyroid cancer is minimizing treatment-related side effects and unnecessary interventions while improving patients’ overall and disease-specific survival rates, reducing the risk of disease persistence or recurrence, and conducting accurate staging and recurrence risk analysis. Appropriate surgical treatment is the most important requirement for this purpose, and additional treatments including radioactive iodine therapy and thyroid-stimulating hormone suppression therapy are performed depending on the patients’ staging and recurrence risk. Diagnostic surgery may be considered when repeated pathologic tests yield nondiagnostic results (Bethesda category 1) or atypia of unknown significance (Bethesda category 3), depending on clinical risk factors, nodule size, ultrasound findings, and patient preference. If a follicular neoplasm (Bethesda category 4) is diagnosed pathologically, surgery is the preferred option. For suspicious papillary carcinoma (suspicious for malignancy, Bethesda category 5), surgery is considered similar to a diagnosis of malignancy (Bethesda category 6). As for the extent of surgery, if the cancer is ≤1 cm in size and clinically free of extrathyroidal extension (ETE) (cT1a), without evidence of cervical lymph node (LN) metastasis (cN0), and without obvious reason to resect the contralateral lobe, a lobectomy can be performed. If the cancer is 1-2 cm in size, clinically free of ETE (cT1b), and without evidence of cervical LN metastasis (cN0), lobectomy is the preferred option. For patients with clinically evident ETE to major organs (cT4) or with cervical LN metastasis (cN1) or distant metastasis (M1), regardless of the cancer size, total thyroidectomy and complete cancer removal should be performed at the time of initial surgery. Active surveillance may be considered for adult patients diagnosed with low-risk thyroid papillary microcarcinoma. Endoscopic and robotic thyroidectomy may be performed for low-risk differentiated thyroid cancer when indicated, based on patient preference.

Background: and Purpose The onset of Huntington’s disease (HD) usually occurs before the age of 50 years, and the median survival time from onset is 15 years. We investigated survival in patients with late-onset HD (LoHD) (age at onset ≥60 years) and the associations of the number of mutant CAG repeats and age at onset (AAO) with survival in patients with HD. Methods: Patients with genetically confirmed HD at six referral centers in South Korea between 2000 and 2020 were analyzed retrospectively. Baseline demographic, clinical, and genetic characteristics and the survival status as at December 2020 were collected. Results: Eighty-seven patients were included, comprising 26 with LoHD (AAO=68.77±5.91 years, mean±standard deviation; 40.54±1.53 mutant CAG repeats) and 61 with common-onset HD (CoHD) (AAO=44.12±8.61 years, 44.72±4.27 mutant CAG repeats). The ages at death were 77.78±7.46 and 53.72±10.86 years in patients with LoHD and CoHD, respectively (p< 0.001). The estimated survival time was 15.21±2.49 years for all HD patients, and 10.74±1.95 and 16.15±2.82 years in patients with LoHD and CoHD, respectively. More mutant CAG repeats and higher AAO were associated with shorter survival (hazard ratio [HR]=1.05, 95% confidence interval [CI]=1.01–1.09, p=0.019; and HR=1.17, 95% CI=1.03–1.31, p=0.013; respectively) for all HD patients. The LoHD group showed no significant factors associated with survival after disease onset, whereas the number of mutant CAG repeats had a significant effect (HR=1.12, 95% CI=1.01–1.23, pp=0.034) in the CoHD group. Conclusions Survival after disease onset was shorter in patients with LoHD than in those with CoHD. More mutant CAG repeats and higher AAO were associated with shorter survival in patients with HD.