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.

In patients with differentiated thyroid cancer (DTC), initial recurrence risk stratification based on clinical, histopathological, and perioperative data remains the key determinant for guiding management strategies during the first 1-2 years post-treatment. However, the adoption of ongoing risk stratification (ORS), which dynamically reassesses risk by integrating longitudinal clinical data and treatment response, enables more precise long-term prognostic assessment and facilitates highly individualized management. Building upon recent guidelines, the 2026 KTA guideline has been further refined by incorporating robust evidence from large-scale national cohorts and comprehensive systematic reviews. These updated recommendations outline contemporary concepts of ORS, risk-adapted TSH suppression targets, optimized surveillance modalities for recurrence detection, and disease-specific long-term follow-up strategies. Reflecting the paradigm shift toward de-escalated treatment, this revision integrates evolved perspectives on TSH suppression intensity, the clinical interpretation of thyroglobulin levels, and tailored follow-up intervals. These evidence-based recommendations aim to minimize unnecessary treatment and excessive surveillance in the large proportion of patients with excellent prognosis after initial therapy, while ensuring that each patient receives appropriately tailored and effective long-term management.

Objective: To investigate the prevalence of pathological findings and clinical outcomes of riskreducing salpingo-oophorectomy (RRSO) in asymptomatic carriers with germline homologous recombination repair (HRR) gene pathogenic/likely pathogenic variants (PV/LPV). Methods: This retrospective study enrolled asymptomatic carriers with germline HR gene PV/ LPV who underwent RRSO between 2006 and 2022 at the National Cancer Center in Korea.Clinical characteristics, including history of breast cancer, family history of ovarian/breast cancer, parity, and oral contraceptive use, were analyzed. Results: Of the 255 women who underwent RRSO, 129 (50.6%) had PV/LPV in BRCA1, 121 (47.5%) in BRCA2, and 2 (0.7%) had both BRCA1 and BRCA2 PV/LPV. In addition, 1 carried PV/ LPV in RAD51D, and 2 in BRIP1. Among the BRCA1/2 PV/LPV carriers, occult neoplasms were identified in 3.5% of patients: serous tubal intraepithelial carcinoma (1.1%, n=3), fallopian tubal cancers (0.8%, n=2), ovarian cancer (1.2%, n=3), and breast cancer (0.4%, n=1). Of the 9 patients with occult neoplasms, 5 (2.0%) were identified from the 178 breast cancer patients, and 4 (1.6%) were detected in 65 healthy mutation carriers. During the median follow-up period of 36.7 months (interquartile range, 25.9–71.4), 1 (0.4%) BRCA1 PV carrier with no precursor lesions at RRSO developed primary peritoneal carcinomatosis after 30.1 months. Conclusion Women with HRR gene mutations PV/LPV who undergo RRSO are at a risk of detecting occult neoplasms, with a of 3.5%. Even in the absence of precursor lesions during RRSO, there was a cumulative risk of peritoneal carcinomatosis development, emphasizing the need for continued surveillance.

Objective: To evaluate the diagnostic performance of susceptibility map-weighted imaging (SMwI) taken in different acquisition planes for discriminating patients with neurodegenerative parkinsonism from those without. Materials and Methods: This retrospective, observational, single-institution study enrolled consecutive patients who visited movement disorder clinics and underwent brain MRI and 18F-FP-CIT PET between September 2021 and December 2021. SMwI images were acquired in both the oblique (perpendicular to the midbrain) and the anterior commissure-posterior commissure (AC-PC) planes. Hyperintensity in the substantia nigra was determined by two neuroradiologists. 18F-FP-CIT PET was used as the reference standard. Inter-rater agreement was assessed using Cohen’s kappa coefficient. The diagnostic performance of SMwI in the two planes was analyzed separately for the right and left substantia nigra. Multivariable logistic regression analysis with generalized estimating equations was applied to compare the diagnostic performance of the two planes. Results: In total, 194 patients were included, of whom 105 and 103 had positive results on 18F-FP-CIT PET in the left and right substantia nigra, respectively. Good inter-rater agreement in the oblique (κ = 0.772/0.658 for left/right) and AC-PC planes (0.730/0.741 for left/right) was confirmed. The pooled sensitivities for two readers were 86.4% (178/206, left) and 83.3% (175/210, right) in the oblique plane and 87.4% (180/206, left) and 87.6% (184/210, right) in the AC-PC plane. The pooled specificities for two readers were 83.5% (152/182, left) and 82.0% (146/178, right) in the oblique plane, and 83.5% (152/182, left) and 86.0% (153/178, right) in the AC-PC plane. There were no significant differences in the diagnostic performance between the two planes (P > 0.05). Conclusion There are no significant difference in the diagnostic performance of SMwI performed in the oblique and AC-PC plane in discriminating patients with parkinsonism from those without. This finding affirms that each institution may choose the imaging plane for SMwI according to their clinical settings.

Background: s/Aims: Reported incidence of extrahepatic bile duct cancer is higher in Asians than in Western populations. Korea, in particular, is one of the countries with the highest incidence rates of extrahepatic bile duct cancer in the world. Although research and innovative therapeutic modalities for extrahepatic bile duct cancer are emerging, clinical guidelines are currently unavailable in Korea. The Korean Society of Hepato-Biliary-Pancreatic Surgery in collaboration with related societies (Korean Pancreatic and Biliary Surgery Society, Korean Society of Abdominal Radiology, Korean Society of Medical Oncology, Korean Society of Radiation Oncology, Korean Society of Pathologists, and Korean Society of Nuclear Medicine) decided to establish clinical guideline for extrahepatic bile duct cancer in June 2021. Methods: Contents of the guidelines were developed through subgroup meetings for each key question and a preliminary draft was finalized through a Clinical Guidelines Committee workshop. Results: In November 2021, the finalized draft was presented for public scrutiny during a formal hearing. Conclusions The extrahepatic guideline committee believed that this guideline could be helpful in the treatment of patients.

Purpose: Notable effectiveness of trastuzumab deruxtecan in patients with human epidermal growth factor receptor 2 (HER2)–low advanced breast cancer (BC) has focused pathologists’ attention. We studied the incidence and clinicopathologic characteristics of HER2-low BC, and the effects of immunohistochemistry (IHC) associated factors on HER2 IHC results. Materials and Methods: The Breast Pathology Study Group of the Korean Society of Pathologists conducted a nationwide study using real-world data on HER2 status generated between January 2022 and December 2022. Information on HER2 IHC protocols at each participating institution was also collected. Results: Total 11,416 patients from 25 institutions included in this study. Of these patients, 40.7% (range, 6.0% to 76.3%) were classified as HER2-zero, 41.7% (range, 10.5% to 69.1%) as HER2-low, and 17.5% (range, 6.7% to 34.0%) as HER2-positive. HER2-low tumors were associated with positive estrogen receptor and progesterone receptor statuses (p < 0.001 and p < 0.001, respectively). Antigen retrieval times (≥ 36 minutes vs. < 36 minutes) and antibody incubation times (≥ 12 minutes vs. < 12 minutes) affected on the frequency of HER2 IHC 1+ BC at institutions using the PATHWAY HER2 (4B5) IHC assay and BenchMark XT or Ultra staining instruments. Furthermore, discordant results between core needle biopsy and subsequent resection specimen HER2 statuses were observed in 24.1% (787/3,259) of the patients. Conclusion The overall incidence of HER2-low BC in South Korea concurs with those reported in previously published studies. Significant inter-institutional differences in HER2 IHC protocols were observed, and it may have impact on HER2-low status. Thus, we recommend standardizing HER2 IHC conditions to ensure precise patient selection for targeted therapy.

Objective: Fall from height (FFH) is a major public health problem that can result in severe injury, disability, and death. This study investigated how the characteristics of jumpers and fallers differ. Methods: This was a retrospective study of FFH patients enrolled in an Emergency Department-based Injury In-depth Surveillance (EDIIS) registry between 2011 and 2018. Depending on whether the injury was intentional, FFH patients who had fallen from a height of at least 1 m were divided into two groups: jumpers and fallers. Patient characteristics, organ damage, and death were compared between the two groups, and factors that significantly affected death were identified using multivariable logistic analysis. Results: Among 39,419 patients, 1,982 (5.0%) were jumpers. Of the jumpers, 977 (49.3%) were male, while 30,643 (81.9%) of fallers were male. The jumper group had the highest number of individuals in their 20s, with the number decreasing as age increased. In contrast, the number of individuals in the faller group rose until reaching their 50s, after which it declined. More thoracoabdominal, spinal, and brain injuries were found in jumpers. The in-hospital mortality of jumpers and fallers was 832 (42.0%) and 1,268 (3.4%), respectively. Intentionality was a predictor of in-hospital mortality, along with sex, age, and fall height, with an odds ratio of 7.895 (95% confidence interval, 6.746–9.240). Conclusion Jumpers and fallers have different epidemiological characteristics, and jumpers experienced a higher degree of injury and mortality than fallers. Differentiated prevention and treatment strategies are needed for jumpers and fallers to reduce mortality in FFH patients.

Background/Aims: Despite the high efficacy of direct-acting antivirals (DAAs), approximately 1–3% of hepatitis C virus (HCV) patients fail to achieve a sustained virological response. We conducted a nationwide study to investigate risk factors associated with DAA treatment failure. Machine-learning algorithms have been applied to discriminate subjects who may fail to respond to DAA therapy. Methods: We analyzed the Taiwan HCV Registry Program database to explore predictors of DAA failure in HCV patients. Fifty-five host and virological features were assessed using multivariate logistic regression, decision tree, random forest, eXtreme Gradient Boosting (XGBoost), and artificial neural network. The primary outcome was undetectable HCV RNA at 12 weeks after the end of treatment. Results: The training (n=23,955) and validation (n=10,346) datasets had similar baseline demographics, with an overall DAA failure rate of 1.6% (n=538). Multivariate logistic regression analysis revealed that liver cirrhosis, hepatocellular carcinoma, poor DAA adherence, and higher hemoglobin A1c were significantly associated with virological failure. XGBoost outperformed the other algorithms and logistic regression models, with an area under the receiver operating characteristic curve of 1.000 in the training dataset and 0.803 in the validation dataset. The top five predictors of treatment failure were HCV RNA, body mass index, α-fetoprotein, platelets, and FIB-4 index. The accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of the XGBoost model (cutoff value=0.5) were 99.5%, 69.7%, 99.9%, 97.4%, and 99.5%, respectively, for the entire dataset. Conclusions Machine learning algorithms effectively provide risk stratification for DAA failure and additional information on the factors associated with DAA failure.

The initial treatment for differentiated thyroid cancer includes appropriate surgery and radioactive iodine (RAI) therapy, followed by thyroid-stimulating hormone (TSH) suppression therapy as long-term management to prevent recurrence. RAI therapy following thyroidectomy has the three main purposes: remnant ablation, adjuvant therapy, and therapy for known disease. To optimize the goals and targets of RAI therapy, postoperative disease assessment, determination of recurrence risk, and consideration of various individual factors are necessary. The objectives of RAI therapy are determined based on the individual’s recurrence risk, and the administered activity of RAI is then determined according to these treatment objectives. Adequate stimulation of serum TSH is necessary before RAI therapy, and recombinant human TSH is widely used because of its advantage in reducing the risk of exacerbation of comorbidities associated with levothyroxine discontinuation and improving patients’ quality of life. Additionally, reducing iodine intake through appropriate low-iodine diet is necessary. Whole-body scans are conducted to assess the disease status after RAI therapy. If planar whole-body scans are inconclusive, additional single-photon emission computed tomography (SPECT)/CT imaging is recommended. Over the past decade, prospective randomized or retrospective clinical studies on the selection of candidates for RAI therapy, administered activity, methods of TSH stimulation, and advantages of SPECT/CT have been published. Based on these latest clinical research findings and recommendations from relevant overseas medical societies, this clinical practice guideline presents the indications and methods for administering RAI therapy after thyroidectomy.

Based on the clinical, histopathological, and perioperative data of a patient with differentiated thyroid cancer (DTC), risk stratification based on their initial recurrence risk is a crucial follow-up (FU) strategy during the first 1–2 years after initial therapy. However, restratifiying the recurrence risk on the basis of current clinical data that becomes available after considering the response to treatment (ongoing risk stratification, ORS) provides a more accurate prediction of the status at the final FU and a more tailored management approach. Since the 2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and DTC, the latest guidelines that include the National Comprehensive Cancer Network clinical practice and European Association for Medical Oncology guidelines have been updated to reflect several recent evidence in ORS and thyroid-stimulating hormone (TSH) suppression of DTC. The current clinical practice guideline was developed by extracting FU surveillance after the initial treatment section from the previous version of guidelines and updating it to reflect recent evidence. The current revised guideline includes recommendations for recent ORS, TSH target level based on risk stratification, FU tools for detection of recurrence and assessment of disease status, and long-term FU strategy for consideration of the disease status. These evidence-based recommendations are expected to avoid overtreatment and intensive FU of the majority of patients who will have a very good prognosis after the initial treatment of DTC patients, thereby ensuring that patients receive the most appropriate and effective treatment and FU options.