Serum uric acid in Korean children and adolescents: reference percentiles and association with metabolic syndrome.

PURPOSE: To establish age/sex-specific reference intervals for serum uric acid and to examine the associations between serum uric acid level and metabolic syndrome (MetS) and its components in Korean children and adolescents. METHODS: We analyzed data for 1,349 subjects aged 10 to 19 years from the Korea National Health and Nutrition Examination Survey 2016-2017. RESULTS: The mean uric acid levels were 5.9±1.3 mg/dL (interquartile range, 5.0-6.8 mg/dL) in males and 4.6±0.9 mg/dL (interquartile range, 3.9-5.2 mg/dL) in females. The mean uric acid level increased significantly from 10-13 years of age in males, but not in females. The overall prevalence of MetS was 5.9% (7.3% in males and 4.3% in females; P=0.022). The prevalences of MetS in the lowest, second, third, and highest quartiles of uric acid level were 4.4%, 3.3%, 6.1%, and 15.2%, respectively, in males (P for trend <0.001) and 1.9%, 0.0%, 4.1%, and 10.9%, respectively, in females (P for trend <0.001). Compared with the lowest quartile of uric acid level, the odds ratio (with 95% confidence interval) for MetS in the highest quartile was 2.897 (1.140-7.361) in males and 5.173 (1.459-18.342) in females. Subjects in the highest quartile exhibited increased risk for abdominal obesity and low high-density lipoprotein cholesterol in both sexes. CONCLUSION: Serum uric acid level is positively associated with MetS and its components abdominal obesity and low high-density lipoprotein cholesterol.

Treatment of pediatric average-risk medulloblastoma using craniospinal irradiation less than 2500 cGy and chemotherapy: single center experience in Korea.

BACKGROUND: Although craniospinal irradiation (CSI) of 2340 cGy plus tumor booster with chemotherapy have been established as a standard treatment of childhood average-risk (AvR) medulloblastoma (MBL) in Western counties, there are a few recent reports in outcomes of AvR MBL using this strategy in Korean and other Asian children. We investigated the outcome of the Korean children with AvR MBL who were treated with CSI <2500 cGy and chemotherapy. METHODS: Between January 2001 and December 2010, clinical characteristics and outcomes of 42 patients who were diagnosed with AvR MBL postoperatively and treated with radiation including CSI <2500 cGy and chemotherapy in Seoul National University Children's Hospital were analyzed. RESULTS: Their median age was 9 years (range: 3-18.8), and 29 were male. Histological subtypes were classic type in 28 patients, nodular/desmoplastic in 7, and large cell/anaplastic (LCA) in 7. All the patients received adjuvant radiotherapy (CSI with median 2340 cGy and booster) and multiagent chemotherapy as the first-line treatment. With a median follow-up of 54 months, 12 patients experienced relapse or progression of the tumor. The 3- and 5-year disease-free survival (DFS) rates were 78.0%±6.5% and 75.0%±6.9%, respectively, and overall survival (OS) rates were 85.3%±5.6% and 76.8%±6.9%, respectively. The LCA subtype was associated with poorer DFS (P=0.023) and OS (P=0.008), compared with non-LCA subtypes. CONCLUSIONS: The outcomes of children and adolescents with AvR MBL treated with radiation including CSI <2500 cGy and chemotherapy, are compatible to those in Western countries; however, the LCA subtype has a poor outcome with this strategy.

Gonadal and Sexual Dysfunction in Childhood Cancer Survivors.

PURPOSE: Few studies have addressed gonadal and sexual dysfunctions in childhood cancer survivors. We evaluated the prevalence rates and risk factors for gonadal failure among adolescent/young adult childhood cancer survivors and their sexual function. MATERIALS AND METHODS: Subjects were childhood cancer survivors aged 15-29 years who had completed therapy more than 2 years ago. Demographic and medical characteristics were obtained from the patients' medical records. In addition, hormonal evaluation and semen analysis were performed and sexual function was evaluated via questionnaire. RESULTS: The study included 105 survivors (57 males, 48 females), of which 61 were adults (age > 19 years) and 44 were adolescents. In both males and females, the proportion of survivors with low sex hormone levels did not differ among age groups or follow-up period. Thirteen female subjects (27.1%) needed sex hormone replacement, while five males subjects (8.8%) were suspected of having hypogonadism, but none were receiving sex hormone replacement. Of 27 semen samples, 14 showed azospermia or oligospermia. The proportion of normospermia was lower in the high cyclophosphamide equivalent dose (CED) group (CED ≥ 8,000 mg/m2) than the low CED group (27.3% vs. 62.5%, p=0.047). Among adults, none were married and only 10 men (35.7%) and eight women (34.3%) were in a romantic relationship. Though a significant proportion (12.0% of males and 5.3% of females) of adolescent survivors had experienced sexual activity, 13.6% had not experienced sex education. CONCLUSION: The childhood cancer survivors in this study showed a high prevalence of gonadal/sexual dysfunction; accordingly, proper strategies are needed to manage these complications.

Characteristics and Outcomes of Second Malignant Neoplasms after Childhood Cancer Treatment: Multi-Center Retrospective Survey.

This retrospective study investigated the clinical characteristics and outcomes of second malignant neoplasms (SMNs) in survivors of childhood cancer from multiple institutions in Korea. A total of 102 patients from 11 institutions who developed SMN after childhood cancer treatment between 1998 and 2011 were retrospectively enrolled. The most common primary malignant neoplasms (PMNs) were central nervous system (CNS) tumors (n = 17), followed by acute lymphoblastic leukemia (n = 16), non-Hodgkin lymphoma (n = 13), and osteosarcoma (n = 12). The most common SMNs were therapy-related myeloid neoplasms (t-MNs; acute myeloid leukemia [AML], 29 cases; myelodysplastic syndrome [MDS], 12 cases), followed by thyroid carcinomas (n = 15) and CNS tumors (n = 10). The median latency period was 4.9 years (range, 0.5-18.5 years). Among 45 patients with solid tumors defined as an SMN, 15 (33%) developed the lesion in a field previously subjected to radiation. The 5-year overall survival (OS) rate of patients with an SMN was 45% with a median follow-up time of 8.6 years. Patients with AML, MDS, and CNS tumors exhibited the poorest outcomes with 5-year OS rates of 18%, 33%, and 32%, respectively, whereas those with second osteosarcoma showed comparable outcomes (64%) to patients with primary counterpart and those with second thyroid carcinoma had a 100% OS rate. Further therapeutic efforts are recommended to improve the survival outcomes in patients with SMNs, especially in cases with t-MNs and CNS tumors.

A Case of Langerhans Cell Histiocytosis Manifested as a Suprasellar Mass.

Langerhans cell histiocytosis (LCH) has diverse clinical manifestations, including intracranial mass lesions. We report a case of LCH that manifested as a suprasellar mass, and initially misdiagnosed as a germ cell tumor. A 29-year-old woman presented with polyuria, polydipsia and amenorrhea. Laboratory findings revealed hypopituitarism with central diabetes insipidus, and a suprasellar mass and a pineal mass were observed on magnetic resonance imaging. Under the clinical impression of a germ cell tumor, the patient was treated with germ cell tumor chemotherapy (cisplatin and etoposide) and radiation therapy without biopsy. After initial shrinkage of the lesions, further growth of the tumor was observed and a biopsy was performed. The histopathology revealed LCH. After chemotherapy according to the LCH III protocol, the tumor disappeared. She is on regular follow up for 5 years without relapse. The present findings indicate that LCH should be included in the differential diagnosis of a suprasellar mass, even in adults, especially when it manifests with diabetes insipidus. This case also underscores the importance of a histopathologic diagnosis in patients with suprasellar tumors before the initiation of a specific therapy, even if the clinical findings are highly suggestive of a specific diagnosis.

Acute Raoultella planticola cystitis in a child with rhabdomyosarcoma of the bladder neck.

Raoultella planticola is a Gram-negative, non-motile, aerobic bacillus. It is an environmental bacteria found in soil and water, and a very rare cause of local or systemic infection in humans. Although some adult cases of R. planticola infection have been reported, childhood local or systemic infection caused by R. planticola is very rare. Reported herein is a rare case of acute cystitis due to R. planticola in a 16-month-old boy with rhabdomyosarcoma of the bladder neck, and a review of the literature.

Diffuse cerebral vasospasm with infarct after intrathecal cytarabine in childhood leukemia.

Although the varied neurotoxicity of intrathecal (IT) chemotherapy for treatment of childhood acute leukemia is well known, most are related to transient post-puncture headache, drug-induced arachnoiditis, or leukoencephalopathy after methotrexate or cytarabine. Cerebral vasospasm leading to acute infarct after IT chemotherapy is very uncommon in children. Reported herein is a rare case of diffuse cerebral vasospasm with subsequent cerebral infarct after IT cytarabine in a 7-year-old boy with acute lymphoblastic leukemia, who successfully recovered with supportive management, and a review of the literature.

Adult-onset sellar and suprasellar atypical teratoid rhabdoid tumor treated with a multimodal approach: a case report.

We report a very rare case of sellar and suprasellar atypical teratoid rhabdoid tumor (ATRT) in a 42-year-old female patient. The tumor was removed subtotally with a transsphenoidal approach. Histopathologic study showed rhabdoid cells with prominent nucleoli and abundant cytoplasm. Immunohistochemistry for INI1 was completely negative in the tumor cells, consistent with ATRT. After surgery, she received radiotherapy including spinal irradiation with proton beam therapy and subsequent chemotherapy, with no evidence of recurrence for more than 2 years. Up to date, this is the 8th case of an adult-onset ATRT in the sellar or suprasellar region. Despite its rarity, ATRTs should be considered in the differential diagnosis of an unclear malignant sellar or suprasellar lesion in adult patients and the treatment strategies for adult ATRT patients could be differentiated from those of pediatric ATRT patients.

A study of docetaxel and irinotecan in children and young adults with recurrent or refractory Ewing sarcoma family of tumors.

BACKGROUND: Patients with Ewing sarcoma family of tumors (ESFT) who are resistant even to salvage chemotherapy, have dismal prognoses and few therapeutic options. Because the docetaxel/irinotecan (DI) combination has not been previously evaluated in ESFT, we prospectively evaluated its use in patients with recurrent or refractory ESFT. METHODS: Patients aged <30 years with ESFT, who failed ≥ third-line therapy, were eligible. They received docetaxel 100 mg/m(2) intravenously on day 1, and irinotecan 80 mg/m(2) on days 1 and 8, of a 21-day cycle up to 15 cycles or until disease progressed. The primary objective was objective response rate (ORR); secondary objectives were progression-free survival (PFS) and safety. RESULTS: We enrolled nine patients (median age: 13 years); four were male. Two patients had recurrent disease and seven had progressive disease. This group had undergone a median of four prior chemotherapy regimens (range: 3-6), and received a total of 51 DI cycles (median: three cycles/per person; range: 1-15 cycles). The nine patients showed one complete response (CR), two partial responses (PRs), one stable disease, and five progressive diseases, for an ORR (CR + PR) of 3/9 (33.3%). Two patients with PR achieved CR with subsequent surgery. Overall median PFS was 2.2 months (range: 0.5-16.9 months). All nine patients had grade 4 neutropenia (100%); grade 3 diarrhea or grade 2/3 neuropathy each occurred in two patients (22%). All toxicities were manageable without serious morbidities or treatment-related mortality. CONCLUSIONS: The DI combination may be effective and tolerable for patients with heavily pre-treated ESFT. TRIAL REGISTRATION: NCT01380275. Registered June 21, 2011.

Huge intrathoracic malignant peripheral nerve sheath tumor in an adolescent with neurofibromatosis type 1.

Malignant peripheral nerve sheath tumor (MPNST) is a rare soft tissue malignancy usually found in patients with neurofibromatosis type 1 (NF1) with a poor outcome. Although MPNST can be found in any part of the body including head and neck or extremities, intrathoracic MPNST with or without NF1 is uncommon, especially in children or adolescents. Reported herein is a case of huge intrathoracic MPNST in a 16-year-old girl with NF1, and a brief review of the literature.

Proton beam therapy reduces the incidence of acute haematological and gastrointestinal toxicities associated with craniospinal irradiation in pediatric brain tumors.

BACKGROUND: The benefits of proton beam craniospinal irradiation (PrBCSI) in children have been extensively reported in dosimetric studies. However, there is limited clinical evidence supporting the use of PrBCSI. We compared the acute toxicity of PrBCSI relative to that of conventional photon beam CSI (PhBCSI) in children with brain tumours. MATERIAL AND METHODS: We prospectively evaluated the haematological and gastrointestinal toxicities in 30 patients who underwent PrBCSI between April 2008 and December 2012. As a reference group, we retrospectively evaluated the medical records of 13 patients who underwent PhBCSI between April 2003 and April 2012. The median follow-up time from starting CSI was 22 months (range 2-118 months). The mean irradiation dose was 32.1 Gy (range 23.4-39.6 Gy) and 29.4 CGE (cobalt grey equivalents; range 19.8-39.6), in the PrBCSI and PhBCSI groups, respectively (p = 0.236). RESULTS: There was no craniospinal fluid space relapse after curative therapy in either group of patients. Thrombocytopenia was less severe in the PrBCSI group than in the PhBCSI group (p = 0.012). The recovery rates of leukocyte and platelet counts measured one month after treatment were significantly greater in the PrBCSI group than in the PhBCSI group (p = 0.003 and p = 0.010, respectively). Diarrhoea was reported by 23% of patients in the PhBCSI group versus none in the PrBCSI group (p = 0.023). CONCLUSIONS: The incidence rates of thrombocytopenia and diarrhoea were lower in the PrBCSI group than in the PhBCSI group. One month after completing treatment, the recovery from leukopenia and thrombocytopenia was better in patients treated with PrBCSI than in those treated with PhBCSI.

Ewing sarcoma/peripheral primitive neuroectodermal tumor in the adrenal gland of an adolescent: a case report and review of the literature.

Ewing sarcoma/peripheral primitive neuroectodermal tumors (ES/pPNETs) typically occur in the long or flat bones, the chest wall, extraskeletal soft tissue, or less frequently, in solid organs. They can arise from anywhere in the body; however, ES/pPNETs arising from the adrenal gland are very rare, especially in children and adolescents. Herein, the authors report a case of an ES/pPNET in the adrenal gland of a 17-year-old girl, who was successfully treated with a multimodal treatment, with a brief review of the pertinent literature.

Langerhans cell histiocytosis in non-twin siblings.

Langerhans cell histiocytosis (LCH), which has unknown pathogenesis, can manifest as many kinds of signs and symptoms at any age. Although its genetic background has not been exactly identified, the familial clustering of this disease has been described in some reports. It is very uncommon, however, in siblings who are not monozygotic or dizygotic twins. Reported herein is a case of LCH in non-twin siblings (younger sister and elder brother) who were diagnosed at 3.3 and 14.5 years of age, respectively, and successfully treated with chemotherapy, with BRAF V600E mutation status, and a brief review of the literature.

Safety and effects of prophylactic defibrotide for sinusoidal obstruction syndrome in hematopoietic stem cell transplantation.

BACKGROUND: Sinusoidal obstruction syndrome (SOS) is a serious complication of hematopoietic stem cell transplantation (HSCT), with a mortality rate of up to 90%. We report our experience on the use of defibrotide for SOS prophylaxis in HSCT. MATERIAL AND METHODS: We retrospectively reviewed data of 49 patients who received defibrotide as SOS prophylaxis during the course of HSCT at the National Cancer Center, Goyang, Korea, between August 2005 and July 2008. RESULTS: Thirty-four patients (69.4%) were classified as a high-risk group for developing SOS. Defibrotide was well-tolerated, without any grade 3 or 4 toxicity. The median value of maximum total bilirubin within 100 days after HSCT was within the normal range. SOS was diagnosed in only 1 patient, who underwent autologous HSCT due to relapsed medulloblastoma. There was no day 100 treatment-related mortality in our study. CONCLUSIONS: Defibrotide appears to be a safe prophylaxis for SOS. This study suggests that it could be effective to use prophylactic defibrotide in advance to improve HSCT outcomes in patients at risk of SOS.

Successful treatment of primary central nervous system lymphoma without irradiation in children: single center experience.

Primary CNS lymphoma (PCNSL) is a very uncommon disease in children, and usually treated by chemotherapy, combined with focal or craniospinal radiotherapy (RT). However, adverse effects of RT are a concern. We evaluated the outcomes of childhood PCNSL, treated with systemic and intrathecal chemotherapy, but without RT. For fifteen years, six patients among 175 of non-Hodgkin lymphoma were diagnosed as PCNSL in Seoul National University Children's Hospital and we analyzed their medical records retrospectively. Their male:female ratio was 5:1, and median age was 10.1 yr. The primary sites were the sellar area in three patients, parietal area in one, cerebellum in one, and multiple areas in one. Their pathologic diagnoses were diffuse large B-cell lymphoma in three patients, Burkitt lymphoma in two, and undifferentiated B-cell lymphoma in one. Five were treated with the LMB96 treatment protocol, and one was treated with the CCG-106B protocol. None had RT as a first-line treatment. One patient had a local relapse and received RT and salvage chemotherapy, without success. No patient had treatment-related mortality. Their estimated 5-yr event-free and overall survival rates were both 83.3%. In conclusion, PCNSL is a rare disease in childhood, but successfully treated by chemotherapy without RT.

Follicular thyroid carcinoma arising after hematopoietic stem cell transplantation in a child with pleuropulmonary blastoma.

BACKGROUND: Pleuropulmonary blastoma (PPB) is a rare and aggressive intrathoracic neoplasm that is associated with other dysplastic or neoplastic conditions. The prognosis, especially of type II (cystic and solid) and type III (solid) PPB, is poor. High-dose chemotherapy (HDC) and hematopoietic stem cell transplantation (HSCT) have been attempted to improve survival rates. We report the development of follicular thyroid carcinoma in a girl who was treated at a young age for PPB. SUMMARY: A 23-month-old girl was evaluated for a clinical diagnosis of pneumonia and was found to have a mass in the left lung that grew rapidly. It was removed and diagnosed as a PPB. At the age of two, she was referred to our hospital for further treatment. She received adjuvant chemotherapy for 6 months but developed a recurred mass in her back at 4.3 years of age. After removal of the mass, she was given a salvage chemotherapy followed by HDC and HSCT but not radiation treatment between 4.4 and 4.9 years of age. At the age of seven, after 2 years without treatment, she presented with multiple thyroid nodules in both lobes that steadily grew over the next 2 years. At the age of nine, she underwent total thyroidectomy, which revealed an invasive follicular carcinoma. She remained without clinical evidence of thyroid cancer for one year since the surgery. Radiation therapy was not administered because of the concerns of causing another malignancy. A literature search combined with the present case indicated that, of the five living patients who had been treated with HDC and HSCT, three developed a follicular thyroid carcinoma. CONCLUSIONS: The high prevalence (3/5, 60%) of follicular thyroid carcinoma in patients with PPB who were treated with HDC and HSCT is striking. This suggests that, in patients with PPB, either HDC or HSCT contributes to the development of thyroid cancer. Clinicians should be advised of the high risk of thyroid carcinoma occurrence when HDC and HSCT are being contemplated in children with PPB.

Statistics of hematologic malignancies in Korea: incidence, prevalence and survival rates from 1999 to 2008.

BACKGROUND: The nationwide statistical analysis of hematologic malignancies in Korea has not been reported yet. METHODS: The Korea Central Cancer Registry and the Korean Society of Hematology jointly investigated domestic incidence rates and prevalence of hematologic malignancies occurred between 1999 and 2008, and analyzed survival rates of patients who were diagnosed between 1993 and 2008. Data of hematologic malignancies from 1993 to 2008 were obtained from the Korean National Cancer Incidence Data base. The crude incidence rates, age-specific incidence rates, age-standardized incidence rates, annual percentage change of incidence, and prevalence from 1999-2008 were calculated. Survival rates for patients diagnosed in 1993-2008 were estimated. RESULTS: In 2008, a total of 8,006 cases of hematologic malignancies were occurred, which comprised 4.5% of all malignancies. In all genders, non-Hodgkin lymphoma, myeloid leukemia, and multiple myeloma were most frequent diseases. In terms of age, ages between 60 and 69 were most prevalent. From 1999 to 2008, the age-standardized incidence rates increased from 10.2 to 13.7, and the annual percentage change was 3.9%. The 5-year survival rate increased from 38.2% during 1993-1995 to 55.2% during 2004-2008. As of January 2009, number of patients with 10-year prevalence was 33,130, and with 5- to 10-year prevalence was 10,515. CONCLUSION: This is the first nationwide statistical report of hematologic malignancies in Korea. It could be used as the basic information to help investigate epidemiologic characteristics, evaluate progress during the past years, and establish future strategies for hematologic malignancies. Periodic statistical analysis of hematologic malignancies in Korea should be continued.

Hemophagocytic lymphohistiocytosis can mimic the superior vena cava syndrome.

We report a case of a 3-year-old boy with hemophagocytic lymphohistiocytosis (HLH), with enlarged cervical lymph nodes causing internal jugular vein compression, who initially presented a condition similar to the superior vena cava syndrome. Laboratory data along with neck node and bone marrow biopsies confirmed the HLH. Genetic analysis revealed the patient to be compound heterozygous for 2 variations of the perforin gene, c.1620 A>G and c.562C>G. This case featuring a rare initial manifestation of HLH that has not been previously reported, points to the necessity of considering this disease when symptoms similar to superior vena cava syndrome are encountered.

Prediction of tumour necrosis fractions using metabolic and volumetric 18F-FDG PET/CT indices, after one course and at the completion of neoadjuvant chemotherapy, in children and young adults with osteosarcoma.

PURPOSE: The utility of combined metabolic and volumetric (18)F-FDG PET/CT indices for predicting tumour necrosis fractions following neoadjuvant chemotherapy has not been extensively studied in osteosarcoma. Furthermore, little is known of the early PET/CT responses after only one chemotherapy course. METHODS: Enrolled in the study were 20 children and young adults with resectable osteosarcoma who had undergone (18)F-FDG PET/CT scans before and after neoadjuvant chemotherapy. Maximum standardized uptake value (mSUV), metabolic tumour volume (MTV), and total lesion glycolysis (TLG) were measured. From among the 20 patients, 14 were prospectively recruited and underwent an additional PET/CT scan after one chemotherapy course. Histopathological necrosis fractions were compared with the above-mentioned PET/CT indices and their ratios. RESULTS: MTV at the SUV threshold of 2 g/ml was closely correlated with the magnetic resonance image volumes before therapy (r = 0.91). In the prospective cohort, five patients were classified as good responders and nine as poor responders. All the metabolic indices (mSUV and its ratio) and combined metabolic/volumetric indices (MTV, TLG, and their ratios) except the mSUV ratio determined after therapy showed significant differences between good and poor responders (P <0.05). Differences were also noted for all of these indices determined after one chemotherapy course. Furthermore, most of these indices determined after therapy as well as after one chemotherapy course had good sensitivity, specificity, positive predictive value and negative predictive value with respect to predicting histological response to chemotherapy. CONCLUSION: In our osteosarcoma patient population, (18)F-FDG PET/CT indices (either combined metabolic/volumetric or metabolic indices) determined after neoadjuvant chemotherapy were useful in predicting tumour responses. This held true after only one chemotherapy course.

Improvement of induction remission rate by modifying the dose of idarubicin for relapsed childhood acute lymphoblastic leukemia.

Relapse is the major cause of treatment failure in acute lymphoblastic leukemia (ALL), yet there is no established treatment for relapsed ALL. To improve the induction remission rate, we modified the dose of idarubicin in the original Children's Cancer Group (CCG)-1884 protocol, and retrospectively compared the results. Twenty-eight patients diagnosed with relapsed ALL received induction chemotherapy according to the CCG-1884 protocol. Complete remission (CR) rate in all patients after induction chemotherapy was 57%. The idarubicin 10 mg/m(2)/week group showed CR rate of 74%, compared with the 22% CR rate of the idarubicin 12.5 mg/m(2)/week group (p=0.010). Remission failure due to treatment-related mortality (TRM) was 44% and 5.2% in the idarubicin 12.5 mg/m(2)/week and 10 mg/m(2)/week groups, respectively (p=0.011). Overall survival (OS) and 4-yr event-free survival (EFS) were 12.8% and 10.3%, respectively. OS and 4-yr EFS were higher in the idarubicin 10 mg/m(2)/week group (19.3% and 15.6%) than in the 12.5 mg/m(2)/week group (0% and 0%). In conclusion, a modified dose of idarubicin from 12.5 mg/m(2)/week to 10 mg/m(2)/week resulted in an improved CR rate in the treatment of relapsed ALL, which was due to lower TRM. However, despite improved CR rate with modified dose of idarubicin, survival rates were unsatisfactory.