Rectal cancer, which accounts for approximately 40% of colorectal cancers, remains a major clinical concern. Recent advances in diagnostic imaging, surgical techniques, radiotherapy, and systemic treatment have steadily improved rectal cancer outcomes. Considering this, the Korean Rectal Cancer Multidisciplinary (KRCM) Committee has aimed to provide clinicians and policymakers with up-to-date, evidence-based clinical practice guidelines to support optimal decision-making, reflecting current evidence, the Korean healthcare context, and patient values and preferences. The Clinical Practice Guidelines for Rectal Cancer version 2.0 were developed through multidisciplinary collaboration with related academic societies, building upon and updating the KRCM Clinical Practice Guidelines version 1.0 (titled “Multidisciplinary guidelines for the management of rectal cancer”). These consensus guidelines of the KRCM were established based on a comprehensive literature review, evidence synthesis, with recommendation development guided by the GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology, and consideration of applicability in real-world clinical practice under the national health insurance system. Each recommendation has been presented with its strength and level of evidence.

Background: Rapid pathogen identification and antibiotic-susceptibility tests (ASTs) are important for treating bloodstream infections. We compared the performance of the QMAC-dRAST and BD Phoenix M50 direct AST (dPhoenix) systems using bacterial pellets prepared from positive blood culture broth and evaluated their impact on treatment modification. Methods: Direct AST results for 106 Enterobacterales isolates were retrospectively reviewed. Conventional broth microdilution was used to calculate categorical agreement (CA), very major error (VME), major error (ME), and minor error (mE). For isolates showing high VMEs in both methods, supplementary tests were performed. Clinical impact was evaluated by calculating the time required to obtain AST results (time-to-result) and observing changes in antibiotics prescribed after performing ASTs. Results: Both systems showed acceptable overall CA, VME, ME, and mE values (QMACdRAST: 93.6%, 1.6%, 0.9%, and 5.3%, respectively; dPhoenix: 93.1%, 0.9%, 0.6%, and 6.2%, respectively). Piperacillin–tazobactam showed high VMEs with QMAC-dRAST (4/20, 20.0%) and dPhoenix (3/20, 15.0%). Colony AST on 13 isolates revealed that QMACdRAST testing yielded lower minimal inhibitory concentrations (MICs) for piperacillin–tazobactam with three isolates, whereas dPhoenix testing yielded higher MICs with two isolates and lower MICs with two isolates. The average time-to-result was 20.8 hr and 30.1 hr for QMAC-dRAST and dPhoenix, respectively (P < 0.001). After AST, the number of optimal treatments increased from 43 (46.7%) to 72 (78.3%) (P < 0.001). Conclusions The QMAC-dRAST and dPhoenix systems provided reliable AST results with a short time-to-result. However, we recommend performing complementary tests, such as the disk diffusion test, for piperacillin–tazobactam.

This study aimed to determine the prevalence of human epidermal growth factor receptor 2 (HER2)–ultralow breast cancer among cases initially classified as HER2 immunohistochemistry (IHC) 0 and assess interobserver variability in interpreting low-level HER2 expression. Methods: In this multicenter retrospective study, all invasive breast cancer cases diagnosed between January and December 2022 across 10 Korean institutions were retrieved. Institutional pathologists reexamined HER2 IHC slides originally reported as IHC 0 according to the 2018 American Society of Clinical Oncology/College of American Pathologists guidelines and reclassified them as HER2-null (0), HER2-ultralow (0+), or HER2-low (1+). Slides from 10% of HER2-null and HER2-ultralow cases were digitized for central review and independently assessed by two pathologists, with discrepancies resolved by consensus. Results: Among 8,026 cases, 2,836 cases (35.5%) were initially reported as IHC 0. Upon re-review, 1,673 (59.0%), 1,139 (40.2%), and 24 (0.8%) cases were reclassified as HER2-null, HER2-ultralow, and HER2-low, respectively. The prevalence of HER2-ultralow breast cancer varied considerably across institutions (23.7%–78.1%). Central review of 268 digitized cases showed concordance in 193 cases (72.0%). Among the 75 discordant cases, 54 tumors (72.0%) were upgraded from HER2-null to HER2-ultralow, and 18 (24.0%) tumors were upgraded from HER2-ultralow to HER2-low. Furthermore, two tumors (2.7%) were downgraded from HER2-ultralow to HER2-null. Conclusions: Approximately 40% of cases initially categorized as IHC 0 were reclassified as HER2-ultralow. The substantial inter-institutional variability observed in interpreting low-level HER2 expression highlights the need for standardized training and quality assurance to ensure accurate identification of patients eligible for HER2-targeted antibody–drug conjugates.

Objective: To evaluate the performance of supplemental automated breast ultrasound (ABUS) added to mammography-based breast cancer screening for women with nondense breasts. Materials and Methods: A retrospective search of radiology databases at two tertiary institutions identified asymptomatic women with nondense breasts who underwent breast cancer screening using both digital mammography (DM) and supplemental ABUS between January 2020 and December 2023. We excluded women without sufficient follow-up data or those without an established final diagnosis, including histopathologic results. The performance measures of DM alone and ABUS combined with DM (ABUS plus DM) were compared. The primary outcome was the cancer detection rate (CDR), and the secondary outcomes were sensitivity and specificity. Subgroup analyses were performed for women with scattered fibroglandular density and almost entirely fatty breasts. Results: A total of 2,904 pairs of screening examinations were performed in 1,683 women (59 ± 10 years), detecting 26 cancers. In comparison with DM alone, ABUS plus DM showed higher CDR (9.0 vs. 7.9 per 1,000 examinations, P < 0.001), higher sensitivity (100% [26/26] vs. 88.5% [23/26], P < 0.001), and lower specificity (95.0% [2,735/2,878] vs. 97.9% [2,817/2,878], P < 0.001). In women with scattered fibroglandular density, ABUS increased the CDR from 7.4 to 8.5 per 1,000 examinations and improved the sensitivity from 87.0% [20/23] to 100% [23/23] (P < 0.001). In women with almost entirely fatty breasts, ABUS plus DM showed the same CDR (16.4 per 1,000 examinations) and sensitivity (100% [3/3]) as DM alone. Three cancers (11.5% [3/26]), all of which were stage T1N0, were detected only by supplemental ABUS. Conclusion Supplemental ABUS improved cancer detection and sensitivity in women with nondense breasts, with the benefits primarily observed in those with scattered fibroglandular density.

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.

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: The male predominance in the incidence of gastric cancer (GC) is established; however, sex differences in the prognosis of GC remain controversial. As such, this study analyzed the prognosis of patients with GC based on age and sex. Materials and Methods: Data from 14,739 patients diagnosed with GC at Seoul National University Bundang Hospital between 2003 and 2023 were analyzed. Baseline characteristics, histological types of GC, overall and GC-specific survival rates (age and stage stratification), and associated risk factors were analyzed. Results: Females were significantly younger (p < 0.001) and exhibited more gastric body cancers (p < 0.001) and tumors with diffuse-type or poorly differentiated histology (p < 0.001) than males. Females exhibited an advantage over males in terms of overall survival (p=0.004), but not in GC-specific survival. However, age stratification revealed significant sex differences, that females < 50 years of age exhibited survival disadvantages (p < 0.001); however, this trend was reversed with age, and females > 60 years exhibited survival advantages (p < 0.001) for both overall and GC-specific survival. This may be explained by the lower ratio of diffuse-type GC as females age. Furthermore, in the analysis according to stage, females with stage IV disease exhibited significant survival disadvantages, with significantly younger age and a higher proportion of diffuse-type GC which exhibits aggressive features, resulting in poorer survival than in males. Conclusion Age and stage stratification revealed significant differences in survival between the sexes, which can be helpful for public health strategies.

Janus kinase (JAK) inhibitors are an important treatment option for ulcerative colitis, providing rapid onset of action, oral administration, and efficacy even after biologic failure. The 3 approved agents—tofacitinib, filgotinib, and upadacitinib—differ in JAK isoform selectivity, leading to clinically meaningful differences in efficacy and safety. Evidence from network meta-analyses, clinical trials, and real-world studies consistently shows that upadacitinib provides the highest efficacy for induction and maintenance of remission, whereas filgotinib demonstrates the most favorable safety profile. The strong efficacy of upadacitinib and tofacitinib is particularly relevant in patients with severe disease, including acute severe ulcerative colitis, and upadacitinib maintains high efficacy regardless of prior advanced therapy exposure. JAK inhibitors also benefit extraintestinal manifestations. Although risks such as herpes zoster, serious infection, thromboembolism, and major cardiovascular events differ among agents, long-term data suggest generally acceptable safety when used appropriately. Intraclass JAK-to-JAK cycling is feasible, with about half of patients achieving steroid-free clinical remission in retrospective cohorts. Based on mechanistic, clinical, and real-world evidence, filgotinib may be a first-line option for patients with lower disease activity or when safety is a priority, whereas upadacitinib or tofacitinib may be preferred in higher disease activity. Strategically selecting agents may improve durability and outcomes.

Background: Cough is a prominent symptom of chronic respiratory diseases, including asthma, idiopathic pulmonary fibrosis (IPF), chronic obstructive pulmonary disease (COPD), and bronchiectasis (BE). Some patients develop chronic cough (CC), defined as lasting more than 8 weeks, yet its characteristics remain poorly understood. This study aimed to characterize CC across various chronic respiratory diseases using validated cough assessment tools. Methods: The Cough Assessment in Chronic Respiratory Diseases (COASESS) study, a multicenter, prospective cross-sectional study, was conducted at 10 university hospitals. CC was evaluated in terms of intensity (numeric rating scale [NRS]), frequency (cough symptom score [CSS]), and quality of life (using the cough assessment test [COAT] and Leicester cough questionnaire [LCQ]). Cough hypersensitivity was assessed with the cough hypersensitivity questionnaire (CHQ). Data on age, sex, and smoking status were also collected. Results: Among the 303 enrolled patients, 266 with chronic respiratory diseases were included in the analysis. Patients with asthma were younger, predominantly female, and non-smokers, whereas those with COPD and IPF were older males who had previously smoked (p<0.001). Scores for COAT, LCQ, NRS, and CSS showed significant differences across the diseases, with asthma and IPF patients experiencing a greater symptom burden and lower quality of life compared to those with COPD or BE (p<0.001). Although CHQ total scores were similar across groups, asthma patients more frequently reported triggers such as talking and post-nasal drip. Conclusion This study revealed distinct characteristics of CC across different chronic respiratory diseases. Asthma and IPF were associated with a higher symptom burden, and cough hypersensitivity varied depending on the underlying condition. These findings highlight the necessity for disease-specific assessments and management strategies for CC.