ABSTRACT
Purpose@#Renal tumors account for approximately 7% of all childhood cancers. These include Wilms tumor (WT), clear cell sarcoma of the kidney (CCSK), malignant rhabdoid tumor of the kidney (MRTK), renal cell carcinoma (RCC), congenital mesoblastic nephroma (CMN) and other rare tumors. We investigated the epidemiology of pediatric renal tumors in Korea. @*Materials and Methods@#From January 2001 to December 2015, data of pediatric patients (0–18 years) newly-diagnosed with renal tumors at 26 hospitals were retrospectively analyzed. @*Results@#Among 439 patients (male, 240), the most common tumor was WT (n=342, 77.9%), followed by RCC (n=36, 8.2%), CCSK (n=24, 5.5%), MRTK (n=16, 3.6%), CMN (n=12, 2.7%), and others (n=9, 2.1%). Median age at diagnosis was 27.1 months (range 0-225.5) and median follow-up duration was 88.5 months (range 0-211.6). Overall, 32 patients died, of whom 17, 11, 1, and 3 died of relapse, progressive disease, second malignant neoplasm, and treatment-related mortality. Five-year overall survival and event free survival were 97.2% and 84.8% in WT, 90.6% and 82.1% in RCC, 81.1% and 63.6% in CCSK, 60.3% and 56.2% in MRTK, and 100% and 91.7% in CMN, respectively (p < 0.001). @*Conclusion@#The pediatric renal tumor types in Korea are similar to those previously reported in other countries. WT accounted for a large proportion and survival was excellent. Non-Wilms renal tumors included a variety of tumors and showed inferior outcome, especially MRTK. Further efforts are necessary to optimize the treatment and analyze the genetic characteristics of pediatric renal tumors in Korea.
ABSTRACT
Cancer predisposition syndromes (CPS) are a group of genetic disorders that increase the risk of developing various types of cancer. The prevalence of CPS in children has been known to be up to 18-20% based on recent reports. However, this number may still be an underestimation. Appropriate surveillance and early detection of cancer is important for improving survival outcomes of patients with CPS, making it important for clinicians to recognize flag signs and refer patients to genetic counselling. Advances in high-throughput sequencing and imaging modalities, such as wholebody MRI, have enabled personalized risk assessment and patient-tailored management of CPS. Optimizing surveillance strategies is also a focus of recent research to minimize risks associated with screening procedures, radiation exposure, and psychological burden on patients and their families. This review aims to provide the latest updates on diagnostic and surveillance strategies for childhood CPS to assist pediatricians in recognizing, referring, and managing children at risk for CPS.
ABSTRACT
With impressive clinical advancements in immune effector cell therapies targeting CD19, chimeric antigen receptor (CAR) T-cell therapy has emerged as a new paradigm for treating relapsed/refractory B-cell malignancies. Currently, three second-generation CAR T-cell therapies have been approved, of which only tisagenlecleucel (tisa-cel) is approved for treating children and young adults with B-cell acute lymphoblastic leukemia (ALL) with durable remission rates of approximately 60‒90%. Although CAR T-cell therapies are considered to treat refractory B-ALL, they are associated with unique toxicities such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). The severity of CAR T-cell therapy toxicities can vary according to several clinical factors. In rare cases, severe CRS can progress to a fulminant hyperinflammatory syndrome known as hemophagocytic lymphohistiocytosis, which has a poor prognosis.The first-line treatments for CRS/ICANS include tocilizumab and corticosteroids. When severe CAR T-cell toxicity is resistant to first-line treatment, an additional approach is required to manage the persistent inflammation. In addition to CRS/ICANS, CAR T-cell therapy can cause early and delayed hematological toxicity, which can predispose patients to severe infections. The use of growth factors and anti-infective prophylaxis should follow institutional guidelines according to patient-specific risk factors. This review provides a thorough summary of updated practical recommendations for managing acute and delayed adverse effects following anti-CD19 CAR T-cell therapy in adults and children.
ABSTRACT
Background@#Allogeneic HSCT may improve survival in pediatric ALL patients who relapse. In this study, we analyzed the outcome and prognostic factors of 62 ALL patients (35 male, 56.5%) who received allogeneic HSCT in second complete remission (CR) at our institution between April 1st 2009 and December 31st 2019. @*Methods@#The median time from diagnosis to relapse was 35.1 months (range, 6.0‒113.6 mo).Fifty-three patients (85.5%) experienced bone marrow relapse only. The number of patients who received transplant according to each donor type was as follows: HLA matched family donor 17 (27.4%), matched unrelated donor (UD) 22 (35.5%), mismatched donor 23 (37.1%). All patients received HSCT with a myeloablative conditioning, 58 patients (93.5%) with the incorporation of TBI [31 patients 12 Gray (Gy), 24 patients 13.2 Gy, 3 patients 8 Gy]. @*Results@#The 5-year event-free survival (EFS), and overall survival of the study group was 41.3±6.3% (26/62), and 42.3±6.6% (27/62), respectively. The cumulative incidence of relapse and transplant-related mortality was 57.1±6.4% and 1.6±1.6%, respectively.Infant ALL, shorter time from diagnosis to relapse, and TBI dose of 12 Gy, rather than 13.2 Gy, resulted in significantly worse EFS. In multivariate analysis, infant ALL and TBI dose of 12 Gy during conditioning predicted significantly lower EFS. @*Conclusion@#In our study group, treatment with a higher dose of TBI during conditioning resulted in better EFS for ALL patients who underwent HSCT in second CR. Further study is needed to determine potential long-term complications associated with a higher TBI dose.
ABSTRACT
Background@#Hodgkin's lymphoma (HL) constitutes 10%–20% of all malignant lymphomas and has a high cure rate (5-year survival, around 90%). Recently, interest has increased concerning preventing secondary complications (secondary cancer, endocrine disorders) in long-term survivors. We aimed to study the epidemiologic features and therapeutic outcomes of HL in children, adolescents, and young adults in Korea. @*Methods@#We performed a multicenter, retrospective study of 224 patients aged < 25 years diagnosed with HL at 22 participating institutes in Korea from January 2007 to August 2016. @*Results@#A higher percentage of males was diagnosed at a younger age. Nodular sclerosis histopathological HL subtype was most common, followed by mixed cellularity subtype.Eighty-one (36.2%), 101 (45.1%), and 42 (18.8%) patients were classified into low, intermediate, and high-risk groups, respectively. Doxorubicin, bleomycin, vinblastine, dacarbazine was the most common protocol (n = 102, 45.5%). Event-free survival rate was 86.0% ± 2.4%, while five-year overall survival (OS) rate was 96.1% ± 1.4%: 98.7% ± 1.3%, 97.7% ± 1.6%, and 86.5% ± 5.6% in the low, intermediate, and high-risk groups, respectively (P = 0.021). Five-year OS was worse in patients with B-symptoms, stage IV disease, highrisk, splenic involvement, extra-nodal lymphoma, and elevated lactate dehydrogenase level.In multivariate analysis, B-symptoms and extra-nodal involvement were prognostic factors for poor OS. Late complications of endocrine disorders and secondary malignancy were observed in 17 and 6 patients, respectively. @*Conclusion@#This is the first study on the epidemiology and treatment outcomes of HL in children, adolescents, and young adults in Korea. Future prospective studies are indicated to develop therapies that minimize treatment toxicity while maximizing cure rates in children, adolescents, and young adults with HL.
ABSTRACT
Mannosylerythritol lipids (MELs) are glycolipids and have several pharmacological efficacies. MELs also show skin-moisturizing efficacy through a yet-unknown underlying mechanism. Aquaporin-3 (AQP3) is a membrane protein that contributes to the water homeostasis of the epidermis, and decreased AQP3 expression following ultraviolet (UV)-irradiation of the skin is associated with reduced skin moisture. No previous study has examined whether the skin-moisturizing effect of MELs might act through the modulation of AQP3 expression. Here, we report for the first time that MELs ameliorate the UVA-induced downregulation of AQP3 in cultured human epidermal keratinocytes (HaCaT keratinocytes). Our results revealed that UVA irradiation decreases AQP3 expression at the protein and messenger RNA (mRNA) levels, but that MEL treatment significantly ameliorated these effects. Our mitogen-activated protein kinase inhibitor analysis revealed that phosphorylation of c-Jun N-terminal kinase (JNK), but not extracellular signal-regulated kinase or p38, mediates UVA-induced AQP3 downregulation, and that MEL treatment significantly suppressed the UVA-induced phosphorylation of JNK. To explore a possible mechanism, we tested whether MELs could regulate the expression of peroxidase proliferator-activated receptor gamma (PPAR-γ), which acts as a potent transcription factor for AQP3 expression. Interestingly, UVA irradiation significantly inhibited the mRNA expression of PPAR-γ in HaCaT keratinocytes, whereas a JNK inhibitor and MELs significantly rescued this effect. Taken together, these findings suggest that MELs ameliorate UVA-induced AQP3 downregulation in HaCaT keratinocytes by suppressing JNK activation to block the decrease of PPAR-γ. Collectively, our findings suggest that MELs can be used as a potential ingredient that modulates AQP3 expression to improve skin moisturization following UVA irradiation-induced damage.
Subject(s)
Humans , Down-Regulation , Epidermis , Glycolipids , Homeostasis , JNK Mitogen-Activated Protein Kinases , Keratinocytes , Membrane Proteins , Peroxidase , Phosphorylation , Phosphotransferases , PPAR gamma , Protein Kinases , RNA, Messenger , Skin , Transcription Factors , WaterABSTRACT
BACKGROUND: Precursor T-cell acute lymphoblastic leukemia (T-ALL) has worse prognosis than B-cell ALL. We aimed to evaluate prognostic variables in pediatric T-ALL. METHODS: Medical records of 36 T-ALL patients (27 males and 9 females; median age at diagnosis, 10.6 years) diagnosed and treated at Asan Medical Center from 2001 to 2017 were reviewed. Six patients (16.7%) had early T-cell precursor ALL (ETP-ALL). Most patients received the Children's Cancer Group-1882 (CCG1882) or Korean multicenter high risk ALL (ALL0601) protocols and prophylactic cranial irradiation. Clinical features at presentation, response to therapy, and treatment outcomes were analyzed. RESULTS: The six patients with ETP-ALL and 17 of 30 with non-ETP-ALL received CCG1882 or ALL0601 chemotherapy. Three patients, including two with ETP-ALL, did not achieve complete remission after induction. Rapid early response during induction was achieved by 26 patients. Five year overall survival (OS) and event free survival (EFS) rates were 71.4% and 70.2%, respectively. ETP-ALL and slow early response during induction were significant adverse prognostic factors, while hyperleukocytosis at diagnosis was not. CCG1882/ALL0601 chemotherapy resulted in superior survival (OS: 78.9%, EFS: 73.3%) compared with CCG1901 chemotherapy (OS: 64.3%, EFS: 64.3%), and patients undergoing prophylactic cranial irradiation had superior EFS to non-radiated patients. CONCLUSION: A high risk ALL protocol with intensified post-remission therapy, including prophylactic cranial irradiation, conferred T-ALL survival outcomes comparable with those of Western studies. Further treatment intensification should be considered for patients with ETP-ALL and slow induction responders. Additionally, CNS-directed treatment intensification, without prophylactic cranial irradiation, is needed.
Subject(s)
Female , Humans , Male , B-Lymphocytes , Cranial Irradiation , Diagnosis , Disease-Free Survival , Drug Therapy , Medical Records , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Precursor Cells, T-Lymphoid , Precursor T-Cell Lymphoblastic Leukemia-Lymphoma , Prognosis , T-LymphocytesABSTRACT
Isolated pulmonary Langerhans cell histiocytosis (LCH) is a very rare disease in childhood. We report a case of a 5-month-old girl with isolated pulmonary LCH, who was transferred due to incidental chest x-ray finding of multiple cystic lesions without any clinical symptoms. Chest computed tomography (CT) finding suggested that pulmonary LCH was likely, but evaluations including lung biopsy were negative. At a follow-up visit three months later, we performed bronchoalveolar lavage (BAL) fluid analysis and confirmed the presence of CD1a-positive cells, thereby confirming diagnosis of pulmonary LCH. After completing eight months of chemotherapy, yearly follow-up evaluations were performed and there has been no evidence of reactivation of the disease for four years. Based on our case, we suggest that BAL with immunohistochemical staining can be a valuable modality to eliminate the possibility of infection and other infiltrating disorders, and diagnose pulmonary LCH in case of suspicious pulmonary lesions.
Subject(s)
Female , Humans , Infant , Biopsy , Bronchoalveolar Lavage , Diagnosis , Drug Therapy , Follow-Up Studies , Histiocytosis, Langerhans-Cell , Lung , Rare Diseases , ThoraxABSTRACT
Isolated pulmonary Langerhans cell histiocytosis (LCH) is a very rare disease in childhood. We report a case of a 5-month-old girl with isolated pulmonary LCH, who was transferred due to incidental chest x-ray finding of multiple cystic lesions without any clinical symptoms. Chest computed tomography (CT) finding suggested that pulmonary LCH was likely, but evaluations including lung biopsy were negative. At a follow-up visit three months later, we performed bronchoalveolar lavage (BAL) fluid analysis and confirmed the presence of CD1a-positive cells, thereby confirming diagnosis of pulmonary LCH. After completing eight months of chemotherapy, yearly follow-up evaluations were performed and there has been no evidence of reactivation of the disease for four years. Based on our case, we suggest that BAL with immunohistochemical staining can be a valuable modality to eliminate the possibility of infection and other infiltrating disorders, and diagnose pulmonary LCH in case of suspicious pulmonary lesions.
Subject(s)
Female , Humans , Infant , Biopsy , Bronchoalveolar Lavage , Diagnosis , Drug Therapy , Follow-Up Studies , Histiocytosis, Langerhans-Cell , Lung , Rare Diseases , ThoraxABSTRACT
PURPOSE: Previously, Kawasaki disease (KD) treatment with low-dose aspirin was administered for 6–8 weeks after the acute phase. However, inflammatory marker levels normalize before 6–8 weeks. In this study, we aimed to investigate the clinical outcome of short-term low-dose aspirin treatment based on inflammatory and thrombotic marker levels. METHODS: We performed a retrospective review of the medical records of patients with KD who were hospitalized at Chungnam National University Hospital between September 2012 and May 2014. When fever subsided, low-dose aspirin treatment was started. Inflammatory (white blood cell count, erythrocyte sedimentation rate, and C-reactive protein) and thrombotic markers (D-dimer) were monitored at follow-ups conducted in 1- to 2-week intervals. The low-dose aspirin administration was terminated when both markers were normalized and no cardiovascular complications were observed. RESULTS: Eighty-four patients with KD (complete KD, n=49; incomplete KD, n=35) were enrolled. The inflammatory and thrombotic marker levels were normalized within 3–4 weeks on average. At the beginning the low-dose aspirin treatment, 9 patients had coronary artery lesions but 75 did not. When the low-dose aspirin administration was terminated at the time the inflammatory marker levels were normalized, no new CALs developed during the follow-up at 6–8 weeks. CONCLUSION: Most of the inflammatory marker levels were normalized within 3–4 weeks after the acute phase of KD. New cardiovascular complications did not develop during the course of the short-term aspirin treatment based on the inflammatory marker levels, clinical findings, and echocardiography.
Subject(s)
Humans , Aspirin , Blood Cell Count , Blood Sedimentation , Coronary Vessels , Echocardiography , Fever , Follow-Up Studies , Inflammation , Medical Records , Mucocutaneous Lymph Node Syndrome , Retrospective StudiesABSTRACT
PURPOSE: Previously, Kawasaki disease (KD) treatment with low-dose aspirin was administered for 6–8 weeks after the acute phase. However, inflammatory marker levels normalize before 6–8 weeks. In this study, we aimed to investigate the clinical outcome of short-term low-dose aspirin treatment based on inflammatory and thrombotic marker levels. METHODS: We performed a retrospective review of the medical records of patients with KD who were hospitalized at Chungnam National University Hospital between September 2012 and May 2014. When fever subsided, low-dose aspirin treatment was started. Inflammatory (white blood cell count, erythrocyte sedimentation rate, and C-reactive protein) and thrombotic markers (D-dimer) were monitored at follow-ups conducted in 1- to 2-week intervals. The low-dose aspirin administration was terminated when both markers were normalized and no cardiovascular complications were observed. RESULTS: Eighty-four patients with KD (complete KD, n=49; incomplete KD, n=35) were enrolled. The inflammatory and thrombotic marker levels were normalized within 3–4 weeks on average. At the beginning the low-dose aspirin treatment, 9 patients had coronary artery lesions but 75 did not. When the low-dose aspirin administration was terminated at the time the inflammatory marker levels were normalized, no new CALs developed during the follow-up at 6–8 weeks. CONCLUSION: Most of the inflammatory marker levels were normalized within 3–4 weeks after the acute phase of KD. New cardiovascular complications did not develop during the course of the short-term aspirin treatment based on the inflammatory marker levels, clinical findings, and echocardiography.
Subject(s)
Humans , Aspirin , Blood Cell Count , Blood Sedimentation , Coronary Vessels , Echocardiography , Fever , Follow-Up Studies , Inflammation , Medical Records , Mucocutaneous Lymph Node Syndrome , Retrospective StudiesABSTRACT
PURPOSE: The effects of gonadotropin-releasing hormone agonist (GnRHa) treatment on the energy metabolism in girls with central precocious puberty (CPP) are controversial. We focused the changes and related factors of serum levels of leptin and adiponectin in girls with CPP before and during GnRHa treatment. METHODS: Thirty girls with idiopathic CPP were enrolled in the study. Their auxological data and fasting blood were collected at the baseline and after six months of GnRHa treatment. RESULTS: After treatment, height (P<0.001), weight (P<0.001), and serum leptin levels (P=0.033) were significantly increased, whereas body mass index (BMI), homeostasis model of assessment-insulin resistance, serum adiponectin levels, and adiponectin/leptin ratio exhibited no significant changes. A Pearson correlation analysis showed that height, weight, BMI, and their standard deviation scores (SDSs), but not basal LH, FSH, and estradiol, were significantly correlated with serum leptin levels before and after GnRHa treatment. After a multiple linear regression analysis, only BMI was associated with serum leptin levels. Moreover, leptin SDSs adjusted for BMI were not significantly different before and after GnRHa. The Δ leptin levels (r2=0.207, P=0.012), but not with Δ leptin SDS (r2=0.019, P=0.556), during GnRHa treatment were positively correlated with Δ BMI. CONCLUSION: These results suggest that GnRHa treatment in girls with CPP does not affect serum levels of leptin and adiponectin and insulin resistance. Serum leptin levels were depend on the changes in BMI during GnRHa treatment.
ABSTRACT
PURPOSE: The effects of gonadotropin-releasing hormone agonist (GnRHa) treatment on the energy metabolism in girls with central precocious puberty (CPP) are controversial. We focused the changes and related factors of serum levels of leptin and adiponectin in girls with CPP before and during GnRHa treatment. METHODS: Thirty girls with idiopathic CPP were enrolled in the study. Their auxological data and fasting blood were collected at the baseline and after six months of GnRHa treatment. RESULTS: After treatment, height (P<0.001), weight (P<0.001), and serum leptin levels (P=0.033) were significantly increased, whereas body mass index (BMI), homeostasis model of assessment-insulin resistance, serum adiponectin levels, and adiponectin/leptin ratio exhibited no significant changes. A Pearson correlation analysis showed that height, weight, BMI, and their standard deviation scores (SDSs), but not basal LH, FSH, and estradiol, were significantly correlated with serum leptin levels before and after GnRHa treatment. After a multiple linear regression analysis, only BMI was associated with serum leptin levels. Moreover, leptin SDSs adjusted for BMI were not significantly different before and after GnRHa. The Δ leptin levels (r2=0.207, P=0.012), but not with Δ leptin SDS (r2=0.019, P=0.556), during GnRHa treatment were positively correlated with Δ BMI. CONCLUSION: These results suggest that GnRHa treatment in girls with CPP does not affect serum levels of leptin and adiponectin and insulin resistance. Serum leptin levels were depend on the changes in BMI during GnRHa treatment.
ABSTRACT
New surgical techniques utilizing computer-aided engineering have been recently developed to improve the quality of surgery and reduce the risk to patients. This paper reports the surgical cases using rapid prototyping assisted orthopeadic fracture surgery (RPAOFS). RPAOFS utilizes the symmetric characteristics of the human body, and the potential for RE and RP in which the physical shape is manufactured repidly from the CT data. The physical shape before the injury was manufactured from the RP using the mirror transformed CAD data of the uninjured extents. Subsequently, pre-operative planning, such as the selection of the proper implant, preforming of the implant, selection of the fixation positions, and surgery are performed utilizing the physical shape. RPAOFS was applied to two cases such as a distal tibia communited fracture and a proximal tibia plateau fracture. The surgical results showed that RPAOFS is an effective surgical tools.
Subject(s)
Humans , Human Body , Surgery, Computer-Assisted , TibiaABSTRACT
Most extended care facilities have admitted both the healthy and unhealthy elderly, among which members' average caring demand vary. The Aged Welfare Law, however, currently provides no reasonable basis on the staffing policy for extended care facilities. It just reflects the admitted number of the elderly rather than differences in members' average caring demand among facilities. This study is designed to estimate the need for caring staff on the basis of the correlation between the individual health status measured by various tools including Activities of Daily Living and caring demand by actual service time for each one. The sample included all of the admitted elderly(187 persons) in 4 extended care facilities, two in Seoul and the other two in KangWon-Do over the survey period October 5 through October 20, 1996. The survey process consisted of 3 stages. (1) The current staffing information was collected through self-completed written questionnaires left for head official in each facility. (2) Six graduate students at School of Public Health interviewed all residents to collect information on their health status and sociodemographics. The response rate for the interview was relatively high(85%). (3) Information on direct and indirect caring time consumed for each residents came from self-completed written questionnaires given to nurses and helpers in each target facilities. Analysis of the data was made using Pearson's correlation and multiple regression technique through SAS program. Based on this procedure, the following was found. 1. No facility meet the staffing standard in the Aged Welfare Law completely. 2. It is actual service time that is most correlated with ADL(Activities of daily living). 3. When all of the elderly are divided by four groups based on the level of ADL, the mean values of needed caring time in each group are 15, 21, 36 and 88 minutes respectively. 4. There is no significant difference among facilities in distribution of elderly person by group. 5. No facility meets the estimated number of nurses and helpers which reflects health status of the admitted elderly. Therefore, it is required that severity of the admitted elderly be considered in establishing staffing standard for extended care facility.
Subject(s)
Aged , Humans , Activities of Daily Living , Head , Jurisprudence , Public Health , Surveys and Questionnaires , Seoul , Skilled Nursing FacilitiesABSTRACT
This study has attempted to show general characteristics of health centre directors who have served the post of directorship during the last 40 years. Of 3,000 such health centre directors, information on about 2,500 directors was collected. While average length of service for health center directors has increased, that of vacancy period has decreased. Rural areas have a shorter average length of service than the urban area. Rural areas have twice longer length of vacancy period per health center. Kangwon-do has the longest average length of vacancy period since 1980(2.79 months/year), and Daejeon has the shortest length of vacancy period(0.21 months/year). Chung-buk has no physician directors. The civil servant's rank for the directorship has promoted from the fifth level to the fourth level since 1990. A comparison between the physician director and non-physician director was made as follows : First, the proportion of physician directors had maintained rather high before 1980s ; 62.5% in 1963, 78.3% in 1970, 70.4% in 1980. It decreased to 44.1% in 1990 and 47.6% in 1997. Instead, non-physician directors has abruptly increased since 1980s(12.4% in 1980, 55.4% in 1990 and 50.8% in 1997). Second, physician directors mainly locate in the urban area(58.0% in 1997), but non-physician directors mainly in the rural area(67.2% in 1997). Third, since 1980, the average length of service for physician directors and for non-physician directors has become similar. Fourth, the mean age of physician directors is 45.1 years, and that of non-physician directors 55.7 years. The latter is 10 years older than the former.