Late effects of medulloblastoma treatment: multidisciplinary approach of survivors.

PURPOSE: Medulloblastoma is one of the brain tumors with increased life expectancy due to improvements in treatment approaches. Besides the promising results, various undesirable effects can be encountered. This study's aim is to review long-term follow-up outcomes of our cases with medulloblastoma. METHODS: Age at diagnosis, histological type of medulloblastoma, resection extension, chemotherapy and radiotherapy schemes, follow-up duration, and endocrinological, neuropsychiatric, cardiological, auditory, and visual examination results were evaluated in 20 patients diagnosed between 2007 and 2018 and followed 5 years and more. RESULTS: Twenty of 53 patients were included to the study. Eleven (55%) were male. Mean age at diagnosis was 6.95 years; mean age at the time of the study was 14 years. Mean follow-up time was 8.95 years. In terms of surgery, 14 (70%) were gross total, 1 (5%) was near total, and 2 (10%) were subtotal resection. In histopathological examination, 14 (70%) were classical medulloblastoma, 4 (20%) were desmoplastic medulloblastoma, and 1 (5%) was anaplastic medulloblastoma. With regard to endocrinological evaluation, 15 (75%) patients had hypothyroidism, 5 (25%) had growth hormone deficiency, 7 (35%) had clinical growth hormone deficiency, and 5 (25%) had sex hormone disorders. In neuropsychiatric examination, 11 (55%) patients had neurological sequelae, 18 (90%) patients had psychiatric issues, and 14 (70%) patients had two or more neuropsychiatric problems simultaneously. One (5%) patient had mitral valve insufficiency. Twelve patients (60%) had hearing loss. According to visual examination, 6 (30%) patients had refraction problem, 4 (20%) had cataract, and 1 (5%) had dry eye. CONCLUSION: Careful monitoring of long-term side effects is important for improving the quality of life of medulloblastoma patients. Besides endocrinological and other somatic sequelae of the disease and treatment, increased neuropsychiatric problems showed us that only cure is not the issue while treating childhood medulloblastoma.

Five Years Follow-up of Opsoclonus-Myoclonus-Ataxia Syndrome-Associated Neurogenic Tumors in Children.

AIM: Opsoclonus-myoclonus-ataxia syndrome (OMAS) is a rare autoimmune disorder. Approximately half of the cases are associated with neuroblastoma in children. This study's aim is to review management of our cases with OMAS-associated neuroblastoma for treatment approach as well as long-term follow-up. METHODS: Age at onset of symptoms and tumor diagnosis, tumor location, histopathology, stage, chemotherapy, OMAS protocol, surgery, and follow-up period were evaluated retrospectively in six patients between 2007 and 2022. RESULTS: Mean age of onset of OMAS findings was 13.5 months and mean age at tumor diagnosis was 15.1 months. Tumor was located at thorax in three patients and surrenal in others. Four patients underwent primary surgery. Histopathological diagnosis was ganglioneuroblastoma in three, neuroblastoma in two, and undifferentiated neuroblastoma in one. One patient was considered as stage 1 and rest of them as stage 2. Chemotherapy was provided in five cases. The OMAS protocol was applied to five patients. Our protocol is intravenous immunoglobulin (IVIG) 1 g/kg/d for 2 consecutive days once a month and dexamethasone for 5 days (20 mg/m2/d for 1-2 days, 10 mg/m2/d for 3-4 days, and 5 mg/m2/d for the fifth day) once a month, alternatively by 2-week intervals. Patients were followed up for a mean of 8.1 years. Neuropsychiatric sequelae were detected in two patients. CONCLUSION: In tumor-related cases, alternating use of corticosteroid and IVIG for suppression of autoimmunity as the OMAS protocol, total excision of the tumor as soon as possible, and chemotherapeutics in selected patients seem to be related to resolution of acute problems, long-term sequelae, and severity.

Is very high platelet count always associated with essential thrombocythemia? An unusual presentation in a child.

Myeloproliferative neoplasms are rare in childhood. They are categorized as Philadelphia chromosome-positive and Philadelphia chromosome-negative. Chronic myeloid leukemia (CML) is the most common myeloproliferative disease in which the Philadelphia chromosome is detected as a result of BCR-ABL rearrangements. In others, the most common genetic abnormality is JAK2V617F mutation. The coexistence of these 2 abnormalities in CML is unexpected, and rare cases have recently been reported in adults. We present a child who had a very high platelet count in which we found this coexistence. The clinical presentation, laboratory findings, management, and prognosis of this coexistence is challenging in such a rare condition.

Central nervous system thrombosis in pediatric acute lymphoblastic leukemia in Turkey: A multicenter study.

BACKGROUND: In patients with acute lymphoblastic leukemia (ALL), the risk of thromboembolism increases due to hemostatic changes secondary to the primary disease and due to treatment-related factors. In this multicenter study, we aimed to research the frequency of central nervous system (CNS) thrombosis occurring during treatment, hereditary and acquired risk factors, clinical and laboratory features of patients with thrombosis, treatment approaches, and thrombosis-related mortality and morbidity rates in pediatric ALL patients. PROCEDURE: Pediatric patients who developed CNS thrombosis during ALL treatment from 2010 to 2021 were analyzed retrospectively in 25 different Pediatric Hematology Oncology centers in Türkiye. The demographic characteristics of the patients, symptoms associated with thrombosis, the stage of the leukemia treatment during thrombosis, the anticoagulant therapy applied for thrombosis, and the final status of the patients recorded through electronic medical records were determined. RESULTS: Data from 70 patients with CNS thrombosis during treatment, out of 3968 pediatric patients with ALL, were reviewed. The incidence of CNS thrombosis was 1.8% (venous: 1.5 %; arterial: 0.03%). Among patients with CNS thrombosis, 47 had the event in the first 2 months. Low molecular weight heparin (LMWH) was the most commonly used treatment with a median of 6 months (min-max: 3-28 months). No treatment-related complications occurred. Chronic thrombosis findings occurred in four patients (6%). In five (7%) patients who developed cerebral vein thrombosis, neurological sequelae (epilepsy and neurological deficit) remained. One patient died related to thrombosis, and the mortality rate was 1.4%. CONCLUSION: Cerebral venous thrombosis and, less frequently, cerebral arterial thrombosis may develop in patients with ALL. The incidence of CNS thrombosis is higher during induction therapy than during other courses of treatment. Therefore, patients receiving induction therapy should be monitored carefully for clinical findings suggestive of CNS thrombosis.

Measurements of Retinal Nerve Fiber Thickness and Ganglion Cell Complex in Neurofibromatosis Type 1, with and Without Optic Pathway Gliomas: A Case Series.

PURPOSE: The aim of this study was to investigate differences in retinal nerve fiber layer (RNFL) and ganglion cell complex (GCC) thicknesses in neurofibromatosis 1 (NF1) cases, with and without optic pathway gliomas (OPGs). MATERIALS AND METHODS: In total, 33 eyes of 33 subjects were evaluated in this prospective observational case series. Twenty-one patients with a diagnosis of NF1 were enrolled. Patients with NF1 and OPGs were included in Group 1 (n = 9), and patients with NF1 without OPGs were included in Group 2 (n = 12). The control group (Group 3) was comprised of 12 age- and sex-matched subjects with no history of ophthalmic or systemic diseases. All of the subjects underwent complete ophthalmic examinations, including best-corrected visual acuity (BCVA), slit lamp microscopy, and indirect ophthalmoscopy. Additionally, optical coherence tomography (OCT) measurements were obtained. RESULTS: There were no statistically significant between-group differences in age and sex (p = 0.227 and 0.986, respectively). The average RNFL thickness in Group 1 (NF1 patients with OPGs) was significantly lower than in Groups 2 and 3 (86.6 ± 22.5, 107.4 ± 6.65, and 108.4 ± 5.05 µm, respectively; p = 0.001). Furthermore, the average GCC thickness in Group 1 was significantly lower than in Groups 2 and 3 (78.6 ± 16.3, 94.8 ± 3.55, and 94.9 ± 3.82 µm, respectively; p < 0.001). CONCLUSIONS: Both RNFL and GCC thicknesses were significantly lower in NF1 patients with OPGs. The use of OCT to quantify damage to the visual pathway may enable earlier detection of OPGs in NF1 patients.

A New Perspective for Infantile Hepatic Hemangioma in the Age of Propranolol: Experience at Baskent University.

Propranolol was first used in 2008 to treat hemangioma; its efficacy and safety have since changed the classical treatment indications. Infantile hepatic hemangioma presents as a spectrum of clinical conditions varying from simple asymptomatic lesions to lethal complications. Tufted hemangioma and Kaposiform hemangioendothelioma are congenital vascular tumors that lead to Kasabach-Merritt syndrome. Hemangiomas, like pure arteriovenous malformations, can cause hyperdynamic heart failure, and diffuse nodular-type hemangiomas can present with hypothyroidism. Respiratory problems and hepatic failure can be associated with diffuse nodular-type liver hemangiomas. There is a spectrum of approaches to management, varying from "watchful waiting" to liver transplant. In the age of propranolol, there has been a prominent change in the infantile hepatic hemangioma treatment algorithm. Our suggestion is early treatment with 3 mg/kg/day propranolol plus 1.0 to1.5 mg/kg/day prednisolone in all patients. This protocol is the most effective strategy for type 3 infantile hepatic hemangioma. Approximately one-third of patients with abdominal compartment syndrome in the era before propranolol treatment required liver transplant; this new treatment obviates transplant for many of these patients.

Secondary Hemophagocytic Lymphohistiocytosis: Do We Really Need Chemotherapeutics for All Patients?

Because of the acute and life-threatening course of the hemophagocytic lymphohistiocytosis (HLH) syndrome, International Histiocyte Society guidelines recommend chemoimmune therapy for the treatment of both primary and secondary HLH (sHLH). To manage children with sHLH, instead of HLH-2004 protocol we considered less immunosuppressive/cytotoxic approach. We assessed 12 children who fulfilled the diagnostic criteria for sHLH between January 2009 and March 2015. Multivariate Cox regression analysis showed that ferritin levels (hazard ratio=1.02, P=0.006), pediatric logistic organ dysfunction scores (hazard ratio=1.01, P=0.001) were the predictors of the survival. The hospital survival was 83% for patients with sHLH who were treated with less immunosuppressive therapy. In conclusion initiation of HLH-specific therapy for the patients with hyperferritinemia-associated sHLH should be delayed while awaiting resolution of systemic inflammation with less immunosuppressive therapy.

A different cause for respiratory disorder in children: cases with pulmonary Langerhans cell histiocytosis.

BACKGROUND AND AIMS: In children, complaints of a respiratory disorder are very frequent. Etiology of respiratory illness is a broad spectrum that varies from a simple viral infection to a malignant disorder. Pulmonary Langerhans cell histiocytosis (PLCH) is one of these entities and it is truly rare in children. The aim of this study is to evaluate our patients with PLCH. METHODS: Patients who had been diagnosed with PLCH were retrospectively evaluated. Features of medical history, onset of the complaints, date of the diagnosis, chest X-Ray and computed tomography (CT) findings, histopathology and other laboratory investigations were considered. RESULTS: There were four cases with PLCH. All of them were male, ages were between 5 months and 16 years. In three cases, major complaints were chronic respiratory problems whereas in one of them there was acute respiratory distress beginning with cough and leading to pneumothorax. In all of the cases, multisystemic involvement was prominent. The diagnosis was proven by histopathology in all of the cases. In two children with smaller age, skin involvement was detected. Time from complaint to diagnosis was minimum 3 months and maximum 3 years. CONCLUSION: PLCH is a rare disorder in children. Pulmonary involvement is generally a component of systemic involvement but in many cases it might have been detected with early respiratory complaints. So, children with chronic respiratory problems should be carefully evaluated and should be followed up for rare entities like PLCH.

A Case of Idiopathic Pulmonary Hemosiderosis Presenting With Signs and Symptoms Mimicking Hemolytic Anemia.

Idiopathic pulmonary hemosiderosis is primarily a disorder of childhood, which is characterized by hemoptysis, iron deficiency anemia, and diffuse parenchymal infiltrates on chest x-ray secondary to recurrent attacks of alveolar hemorrhage. It can be diagnosed by showing hemosiderin laden macrophages in bronchoalveolar lavage fluid after other specific causes of diffuse alveolar hemorrhage are definitely excluded. A 5-year-old male patient was admitted to our clinic with sudden-onset pallor during iron therapy given for anemia. While he was being investigated for clinical and laboratory signs mimicking hemolytic anemia, he developed cough and dyspnea. He had infiltrates on chest x-ray and scattered patchy infiltrates in both lungs on high-resolution computed tomography. Hemosiderin laden macrophages were identified in fasting gastric juice and bronchoalveolar lavage fluid. The patient was diagnosed with idiopathic pulmonary hemosiderosis and started corticosteroid therapy.

Tuberous sclerosis complex; single center experience.

AIM: This study was planned with the aim of retrospectively reviewing the clinical and laboratory findings and therapies of our patients diagnosed with tuberous sclerosis and redefining the patients according to the diagnostic criteria revised by the 2012 International Tuberous Sclerosis Complex Consensus Group and comparing them with the literature. MATERIALS AND METHOD: Twenty patients diagnosed with tuberous sclerosis complex in the Pediatric Neurology Clinic were examined retrospectively in terms of clinical findings and therapies. The diagnoses were compared again according to 1998 and 2012 criteria. RESULTS: It was observed that the complaint at presentation was seizure in 17 of 20 patients and hypopigmented spots on the skin in 3 of 20 patients. On the initial physical examination, findings related with the disease were found in the skin in 17 of the patients, in the eye in 5, in the kidneys in 7 and in the brain with imaging in 17. No cardiac involvement was observed in the patients. Infantile spasm was observed in 7 of the patients who presented because of seizure (n=17), partial seizure was observed in 7 and multiple seizure types were observed in 3. It was found that sirolimus treatment was given to 9 of 20 patients because of different reasons, 7 of these 9 patients had epileptic seizures and sirolimus treatment had no effect on epileptic seizures. According to 2012 diagnostic criteria, no marked change occured in the diagnoses of our patients. CONCLUSIONS: It was observed that the signs and symptoms of our patients were compatible with the literature. Molecular genetic examination was planned for the patients who were being followed up because of probable tuberous sclerosis complex. It was observed that sirolimus treatment had no marked effect on the seizure frequency of our patients.

Serum neuron-specific enolase levels in preterm and term newborns and in infants 1-3 months of age.

BACKGROUND: Elevated serum levels of neuron-specific enolase (NSE) was initially assumed to be specific to neuronal tumors (particularly neuroblastoma), but is now known to accompany nontumoral conditions and tumors other than neuroblastomas. There is a need to establish normal ranges for NSE, especially in early infancy. The aims of this study were to determine reference values for NSE in newborns and young infants and to assess whether NSE levels in early infancy (i.e., preterm infants and term infants) differ from the adult reference range for this enzyme. METHODS: We enrolled 140 healthy babies, which included 40 preterm newborns (3-15 days old and born at 28-42 weeks gestation), 40 term newborns (< 1 month old and born at term), and 60 young infants 1-3 months old (n = 20 per subgroup of 1-, 2-, and 3-month-old infants). The determination of NSE levels was performed by the electrochemiluminescence immunoassay (ECLIA) method using the Elecysys 2010 device (Roche Diagnostics, Mannheim, Germany). The mean serum NSE levels for the preterm newborns was 21.83 ± 15.06 ng/mL [95% confidence interval (95%CI), 16.95-26.71 ng/mL]; term newborns, 18.06 ± 12.83 ng/mL (95%CI, 13.94-22.19 ng/mL); and young infants, 9.09 ± 4.38 ng/mL (95%CI, 7.96-10.23 ng/mL). The mean serum NSE level for infants 1-3 months old was within the ECLIA kit's normal range (4.7-18 ng/mL for adults), whereas the corresponding means for the preterm and term newborns were higher (p < 0.001, for both). CONCLUSION: Our findings suggest that adult reference values should not be applied to the preterm and term age groups.

Complications of total implantable access ports and efficacy of Taurolidine-citrate lock solution against catheter-related infections.

BACKGROUND: Totally, implantable access ports (TIAPs) are used for long standing venous catheterization. This study was designed to present our experiences of the TIAPs applications and efficacy of Taurolidine-citrate lock solution (TCLS) against catheter-related infections. MATERIALS AND METHODS: We evaluated records of the 108 patients implanted with 112 TIAPs, which had been performed using heparin solution or TCLS between 2005 and 2013. RESULTS: Duration of exposure to TIAPs was 17-2051 days (median: 411 days). The primary diagnoses were solid tumours (n = 57), lymphoma (n = 23), haematologic diseases (n = 23), nephrotic syndrome (n = 4), Hirschsprung disease (n = 1). The right external jugular vein was most frequently used vascular access route (72.3%). Mechanical complications were observed in four cases. TIAPs were removed due to remission in 19 cases and infection in 19 cases. Median time from implantation and to the development of infection was 60 days. Heparin solution had been used for care in 33 ports, whereas heparin and TCLS had been used in 79 ports. Based on statistical comparison, use of TCLS was considered to be an important factor for preventing infection (P = 0.03). CONCLUSION: We consider that TCLS reduces infection prevalence so TIAPs would be used more extensively and effectively to prevent infections.

Infectious complications and conservative treatment of totally implantable venous access devices in children with cancer.

Besides their complications, totally implantable venous access devices (TIVADs) increase the quality of life in children with cancer. The aim of this study was analysis of infectious complications and results of conservative management in TIVADs. Three hundred and one catheters were implanted in 283 patients between February 1991 and January 2005. Infectious complications were analyzed retrospectively. Cumulative duration of implantation was 153,757 days. In 140 devices (46.5%), no complication was detected. Total rate of infection was 1.96/1000 catheter days. Types of infections were as follows: catheterrelated bloodstream infections: 190; catheter-related systemic infections: 74; pocket infections: 19, exit site infections: 14; and tunnel infections: 5. Staphylococcus epidermidis and non-albicans candida were the most common isolations. During follow-up, a total of 119 catheters had been removed. Most of them were due to infection (n=42). In conclusion, TIVADs are important in children with cancer who need prolonged intravenous access, so they should be used carefully and managed conservatively in case of complications.

Central retinal artery occlusion in a 13-year-old child as a presenting sign of hyperhomocysteinemia together with high lipoprotein(a) level.

BACKGROUND: We describe a child with central retinal artery occlusion and hyperhomocysteinemia. METHODS: A 13-year-old girl developed sudden vision loss and was hospitalized for diagnosis and treatment. RESULTS: Her physical examination was normal except for her ophthalmologic examination. Her serum homocysteine level and lipoprotein(a) were elevated to 45.27 µmol/L and 61 mg/dL 0-29 mg/dL, respectively. A homozygous mutation was identified for methylenetetrahydrofolate reductase at position C677T. CONCLUSION: This report documents central retinal artery occlusion associated with the risk factors of hyperhomocysteinemia caused by methylenetetrahydrofolate reductase C677 T mutation and high lipoprotein(a) level in a child. Retinal artery occlusion is rare in children. This patient emphasizes the need for a systemic evaluation for hyperhomocysteinemia and lipoprotein(a) levels in children with retinal vascular occlusion of uncertain etiology.

Diencephalic tumors in children: a 30-year experience of a single institution.

PURPOSE: The purpose of this study is to determine the clinical behavior, treatment modalities, and outcome of different histopathological subgroups of diencephalic tumors in children. METHODS: Between 1972 and 2002, 150 children with diencephalic central nervous system tumors were retrospectively analyzed. Surgery was used as primary treatment modality if possible. Chemotherapy regimens consisting of lomustine (CCNU), cisplatin + etoposide, cyclophosphamide + vincristine + procarbazine + prednisolone, and bleomycin + etoposide + cisplatin were used since 1972. Radiotherapy was used in high-grade tumors and in low-grade gliomas in the case of residual or recurrent disease. Mean and median values were used for demographic characteristics. Comparison of survival curves for different groups was performed with log-rank analysis. Tumor subtype and chemotherapy regimens were analyzed using Kaplan-Meier method. RESULTS: Age range was 0.1-17 years (median, 7.5 years) with a male to female ratio of 1.1. Low-grade gliomas were 45.3% of the whole group. Optic pathways were the major site of origin (52.7%). Neurofibromatosis type 1 was diagnosed in 19.3%. A hundred and twenty-nine patients were eligible for survival analysis. At 10 years, overall survival (OS) rate was 74.6%, and the event-free survival (EFS) rate was 43.5% in the whole group. The OS and EFS rates of low-grade glial tumors at 10 years were 98% and 52.8%, respectively. CONCLUSION: The majority of the cases were low-grade gliomas in the diencephalon. The prognosis of the tumors extended in the diencephalon, thalamus, and pineal region was worse than the tumors at optic pathways and hypothalamus.