Background: We aimed to evaluate long-term outcomes of gamma knife radiosurgery (GKS) for cerebral cavernous malformations (CCMs). Methods: Among the 233 CCM patients who underwent GKS, 79 adult patients (96 lesions) followed for over 10 years were included and analyzed retrospectively. Annual hemorrhage rate (AHR) was analyzed the entire cohort of 233 patients and the subset of 79 enrolled patients by dividing lesions into overall CCM lesions and brainstem lesions. AHR, neurologic outcome, adverse radiation effect (ARE), and changes of lesions in magnetic resonance imaging (MRI) were compared before and after GKS. Cox-regression analysis was performed to identify risk factors for hemorrhage following GKS. Results: Mean follow-up duration of 79 enrolled patients was 14 years (range, 10–23 years).The AHR of all CCMs for entire cohort at each time point was 17.8% (pre-GKS), 5.9% (≤ 2 years post-GKS), 1.8% (≤ 10 years post-GKS). The AHR of all CCM for 79 enrolled patients was 21.4% (pre-GKS), 3.8% (2 years post-GKS), 1.4% (10 years post-GKS), and 2.3% (> 10 years post-GKS). The AHR of brainstem cavernous malformation (CM) for entire cohort at each time point was 22.4% (pre-GKS), 10.1% (≤ 2 years post-GKS), 3.2% (≤ 10 years post-GKS). The AHR of brainstem CM for 79 enrolled patients was 27.2% (pre-GKS), 5.8% (2 years post-GKS), 3.4% (10 years post-GKS), and 3.5% (> 10 years post-GKS). Out of the 79 enrolled patients, 35 presented with focal neurologic deficits at the initial clinical visit. Among these patients, 74.3% showed recovery at the last follow-up. Symptomatic ARE occurred in five (6.4%) patients. No mortality occurred. Most lesions were decreased in size at the last follow-up MRI. Previous hemorrhage history (hazard ratio [HR], 8.38; 95% confidence interval [CI], 1.07–65.88; P = 0.043), and brainstem location (HR, 3.10; 95% CI, 1.26–7.64; P = 0.014) were significant risk factors for hemorrhage event. Conclusion GKS for CCM showed favorable long-term outcomes. GKS should be considered for CCM, especially when it has a previous hemorrhage history and brainstem location.

Background: Treatment for large (> 10 mL) arteriovenous malformations (AVMs) remains highly challenging. This study evaluated long-term effect of time-staged gamma knife radiosurgery (GKS) for large AVMs. Methods: For patients with large AVMs treated by time-staged GKS over 10 years, timestaged GKS was repeated every three years targeting the entire nidus if total obliteration was not achieved. Obliteration rate and post-GKS complications were assessed based on 10 mL volume interval of AVMs. Prognostic factors for these outcomes were evaluated using Cox regression analysis. Results: Ninety-six patients were analyzed. For AVMs in the 10–20 mL subgroup, a dose ≥ 13.5Gy yielded higher obliteration rate in the first GKS. In the 20–30 mL subgroup, a second GKS significantly boosted obliteration. AVMs > 30 mL did not achieve any obliteration with the first GKS. Among 35 (36.4%) cases lost to follow-up, 7 (7.2%) were lost due to GKS complications. Kaplan-Meier analysis showed that each subgroup needed different time for achieving 50% favorable obliteration outcome rate: 3.5, 6.5, and 8.2 years for 10–20 mL, 20–30 mL, and > 30 mL subgroup, respectively. Total obliteration rate calculated by intention-to-treat method: 73%, 51.7%, 35.7%, respectively, 61.5% overall. Post-GKS hemorrhage and chronic encapsulated expanding hematoma (CEEH) occurred in 13.5% and 8.3% of cases, respectively.Two patients died. Dose and volume were significant prognostic factors for obliteration. Initial AVM volume was a significant prognostic factor of post-GKS hemorrhage and CEEH. Conclusion Time-staged GKS for large AVMs less than 30 mL has highly favorable long-term outcome and a tolerable complication rate.

Background: Since the long-term outcomes of 162 patients who underwent gamma knife radiosurgery (GKS) as an initial or adjuvant treatment for acoustic neuromas (ANs) with unilateral hearing loss were first reported in 1998, there has been no report of a comprehensive analysis of what has changed in GKS practice. Methods: We performed a retrospective study of the long-term outcomes of 106 patients with unilateral sporadic ANs who underwent GKS as an initial treatment. The mean patient age was 50 years, and the mean initial tumor volume was 3.68 cm 3 (range, 0.10–23.30 cm 3 ).The median marginal tumor dose was 12.5 Gy (range, 8.0–15.0 Gy) and the median follow-up duration was 153 months (range, 120–216 months). Results: The tumor volume increased in 11 patients (10.4%), remained stationary in 27 (25.5%), and decreased in 68 patients (64.2%). The actuarial 3, 5, 10, and 15-year tumor control rates were 95.3 ± 2.1%, 94.3 ± 2.2%, 87.7 ± 3.2%, and 86.6 ± 3.3%, respectively.The 10-year actuarial tumor control rate was significantly lower in the patients with tumor volumes of ≥ 8 cm 3 (P = 0.010). The rate of maintaining the same Gardner-Robertson scale grade was 28.6%, and that of serviceable hearing was 46.4%. The rates of newly developed facial and trigeminal neuropathy were 2.8% and 4.7%, respectively. The patients who received marginal doses of less than 12 Gy revealed higher tumor control failure rates (P = 0.129) and newly occurred facial or trigeminal neuropathy rates (P = 0.040 and 0.313, respectively). Conclusion GKS as an initial treatment for ANs could be helpful in terms of tumor control, the preservation of serviceable hearing, and the prevention of cranial neuropathy. It is recommended to perform GKS as soon as possible not only for tumor control in unilateral ANs with hearing loss but also for hearing preservation in those without hearing loss.

Background: Several cases of pediatric acute hepatitis of unknown etiology related to adenoviral infections have been reported in Europe since January 2022. The aim of this study was to compare the incidence, severity, possible etiology, and prognosis of the disease with those in the past in Korea. Methods: The surveillance group collected data between May and November 2022 using a surveillance system. Acute hepatitis of unknown etiology was defined in patients aged < 16 years with a serum transaminase level > 500 IU/L, not due to hepatitis A-E or other underlying causes. For comparison, data from 18 university hospitals were retrospectively collected as a control group between January 2021 and April 2022. Results: We enrolled 270 patients (mean age, 5 years). The most common symptom was fever. However, the incidence was similar between 2021 and 2022. Liver function test results, number of patients with acute liver failure (ALF), liver transplantation (LT), death, and adenovirus detection rates did not differ between the two groups. None of the adenoviruspositive patients in either group experienced ALF, LT, or death. In the surveillance group, adenovirus-associated virus-2 was detected in four patients, one of whom underwent LT. Patients with an unknown etiology showed significantly higher bilirubin levels, a lower platelet count, and a higher LT rate than patients with a possible etiology. Conclusion The incidence of pediatric acute hepatitis of unknown etiology and adenovirus detection rate have not increased in Korea.

Purpose: We aimed to investigate the risk factors and patterns of locoregional recurrence (LRR) after radical nephrectomy (RN) in patients with locally advanced renal cell carcinoma (RCC). Materials and Methods: We retrospectively analyzed 245 patients who underwent RN for non-metastatic pT3-4 RCC from January 2006 to January 2016. We analyzed the risk factors associated with poor locoregional control using Cox regression. Anatomical mapping was performed on reference computed tomography scans showing intact kidneys. Results: The median follow-up duration was 56 months (range, 1 to 128 months). Tumor extension to renal vessels or the inferior vena cava (IVC) and Fuhrman’s nuclear grade IV were identified as independent risk factors of LRR. The 5-year actuarial LRR rates in groups with no risk factor, one risk factor, and two risk factors were 2.3%, 19.8%, and 30.8%, respectively (p < 0.001). The locations of LRR were distributed as follows: aortocaval area (n=2), paraaortic area (n=4), retrocaval area (n=5), and tumor bed (n=11). No LRR was observed above the celiac axis (CA) or under the inferior mesenteric artery (IMA). Conclusion Tumor extension to renal vessels or the IVC and Fuhrman’s nuclear grade IV were the independent risk factors associated with LRR after RN for pT3-4 RCC. The locations of LRR after RN for RCC were distributed in the tumor bed and regional lymphatic area from the bifurcation of the CA to that of the IMA.

Chronic spontaneous urticaria (CSU) is defined as the occurrence of spontaneous wheals, angioedema, or both for >6 weeks in the absence of specific causes. It is a common condition associated with substantial disease burden both for affected individuals and societies in many countries, including Korea. CSU frequently persists for several years and requires high-intensity treatment; therefore, patients experience deteriorations in quality of life and medication-associated complications. During the last decade, there have been major advances in the pharmacological treatment of CSU and there is an outstanding need for evidence-based guidelines that reflect clinical practice in Korea. The guidelines reported here represent a joint initiative of the Korean Academy of Asthma, Allergy and Clinical Immunology and the Korean Dermatological Association, and aim to provide evidence-based guidance for the management of CSU in Korean adults and children. In Part 1, disease definition, guideline scope and development methodology as well as evidence-based recommendations on the use of antihistamines and corticosteroids are summarized.

Chronic spontaneous urticaria (CSU) is defined as the occurrence of spontaneous wheals, angioedema, or both for >6 weeks in the absence of specific causes. It is a common condition associated with substantial disease burden both for affected individuals and societies in many countries, including Korea. CSU frequently persists for several years and requires high-intensity treatment; therefore, patients experience deteriorations in quality of life and medication-associated complications. During the last decade, there have been major advances in the pharmacological treatment of CSU and there is an outstanding need for evidence-based guidelines that reflect clinical practice in Korea. The guidelines reported here represent a joint initiative of the Korean Academy of Asthma, Allergy and Clinical Immunology and the Korean Dermatological Association, and aim to provide evidence-based guidance for the management of CSU in Korean adults and children. In Part 1, disease definition, guideline scope and development methodology as well as evidence-based recommendations on the use of antihistamines and corticosteroids are summarized.

Background/Aims: For metastatic renal cell carcinoma (RCC), various prognostic scoring systems have been developed. However, owing to the low prevalence of nonclear cell RCC, the three most commonly used tools were mainly developed based on patients with clear cell histology. Accordingly, this study applied three prognostic models to Korean non-clear cell RCC patients treated with first-line temsirolimus. Methods: This study analyzed data for 74 patients with non-clear cell RCC who were treated with temsirolimus as the first-line therapy at eight medical centers between 2011 and 2016. The receiver-operating characteristic (ROC) curves for the different prognostic models were analyzed. Results: Twenty-seven (36.5%), 24 (32.4%), and 44 patients (59.5%) were assigned to the poor prognosis groups of the Memorial Sloan-Kettering Cancer Center (MSKCC), International Metastatic RCC Database Consortium (IMDC), and Advanced Renal Cell Carcinoma (ARCC) risk stratification models, respectively. All three prognostic models reliably discriminated the risk groups to predict progression-free survival and overall survival (p < 0.001). The area under the ROC curve (AUC) for progression and survival was highest for the ARCC model (0.777; 0.734), followed by the IMDC (0.756; 0.724) and the MSKCC (0.742; 0.712) models. Furthermore, the sensitivity and specificity for predicting progression were highest with the ARCC model (sensitivity 63.6%, specificity 85.7%), followed by the MSKCC (sensitivity 58.2%, specificity 86.5%) and the IMDC models (sensitivity 56.4%, specificity 85.7%). Conclusions All three prognostic models accurately predicted the survival of the non-clear cell RCC patients treated with temsirolimus as the first-line therapy. Furthermore, the ARCC risk model performed better than the other risk models in predicting survival.

Objective: The purpose of this study is to investigate an association between sex-hormone exposure during fetal period and the development of Alzheimer’s disease (AD). Methods: Twenty four AD patients and 25 normal controls were included from Memory Impairment Clinic of Pusan National University Hospital in Korea. Subjects are measured the ratio of the length of the second to the fourth digit (2D/4D) to estimate fetal sex-hormone exposure. Analysis of covariance was used to investigate an association between fetal sex-hormone exposure and the development of AD after adjusting age, education level, Korean Mini-Mental Status Examination and head circumference. Results: We found that the females with AD had significantly lower 2D/4D ratios than the female controls. In the females withAD, the 2D/4D ratios in the left hand was 0.021 and 0.017 in the right hand compared with the controls. Conclusion Our findings suggest that the development of AD in female may be related with higher testosterone and lower es-trogen exposure during fetal period.

PURPOSE: Head and neck squamous cell carcinoma (HNSCC) is a deadly disease in which precision medicine needs to be incorporated. We aimed to implement next-generation sequencing (NGS) in determining actionable targets to guide appropriate molecular targeted therapy in HNSCC patients. MATERIALS AND METHODS: Ninety-three tumors and matched blood samples underwent targeted sequencing of 244 genes using the Illumina HiSeq 2500 platform with an average depth of coverage of greater than 1,000×. Clinicopathological data from patients were obtained from 17 centers in Korea, and were analyzed in correlation with NGS data. RESULTS: Ninety-two of the 93 tumors were amenable to data analysis. TP53 was the most common mutation, occurring in 47 (51%) patients, followed by CDKN2A (n=23, 25%), CCND1 (n=22, 24%), and PIK3CA (n=19, 21%). The total mutational burden was similar between human papillomavirus (HPV)–negative vs. positive tumors, although TP53, CDKN2A and CCND1 gene alterations occurred more frequently in HPV-negative tumors. HPV-positive tumors were significantly associated with immune signature-related genes compared to HPV-negative tumors. Mutations of NOTCH1 (p=0.027), CDKN2A (p < 0.001), and TP53 (p=0.038) were significantly associated with poorer overall survival. FAT1 mutations were highly enriched in cisplatin responders, and potentially targetable alterations such as PIK3CA E545K and CDKN2A R58X were noted in 14 patients (15%). CONCLUSION: We found several targetable genetic alterations, and our findings suggest that implementation of precision medicine in HNSCC is feasible. The predictive value of each targetable alteration should be assessed in a future umbrella trial using matched molecular targeted agents.
Biomarkers ; Carcinoma, Squamous Cell* ; Cisplatin ; Epithelial Cells* ; Head* ; Humans ; Korea ; Molecular Targeted Therapy ; Neck* ; Precision Medicine ; Statistics as Topic