Infantile Hemangiomas of the Head and Neck: A Single-Center Experience.

Background: Infantile hemangiomas (IHs) are the most common benign vascular tumors of infancy. Methods: We report our experiences with 248 patients with head and neck IHs. Results: The median admission age was 4 months, and the female/male ratio was 2.18. Among the cases, 45% were followed by no treatment. No local complications were observed in any of these patients. Propranolol was provided to all patients who received medical treatment. The median duration of treatment was 12 months (1-30 months), and the median follow-up period of all patients was 14 months (0-118 months). The treatment response was 98%. The complication rate was 17%, and children aged between 3 and 9 months accounted for 60% of the patients who developed complications. Most of the complications were local complications, such as ulceration and bleeding. Conclusions: Although most IHs regress spontaneously, complications may occur. Propranolol alone is an effective treatment option, and early treatment initiation increases the success rate.

Pediatric paravertebral tumors: analysis of 96 patients.

PURPOSE: The most important complication of paravertebral tumors is cord compression (CC), which is an oncologic emergency. Early and appropriate intervention is important in terms of reducing morbidity and mortality. Here, we report our clinical experience with paravertebral tumors. METHODS: The files of patients who were followed up for benign/malignant paravertebral tumors between 1988 and 2022 were evaluated retrospectively. RESULTS: There were 96 patients with paravertebral tumors. The median age at diagnosis was 5 years (1 month-17 years). The male/female ratio was 1.13. The median time to diagnosis was 4 weeks (0-28 weeks). The most common presenting complaint was pain (62.5%). The diagnosis distribution was as follows: sympathetic nervous system (SNS) tumors (n: 38), soft tissue sarcomas (STS) (n: 23), Langerhans cell histiocytosis (LCH) (n: 12), central nervous system (CNS) tumors (n: 9), germ cell tumor (n: 6), lymphomas (n: 4), and benign tumors (n: 4). Sixty-five patients (67.7%) had CC, 40% of whom received chemotherapy as first-line treatment. Decompression surgery was performed in 58.5% of the patients. For patients with CC, 26 patients had advanced disease at admission. Serious neurologic sequelae were observed in seventeen (17.7%) patients. CONCLUSION: Pain and neurological findings in childhood are warning signs for paravertebral tumors and CC. A detailed neurologic examination and radiodiagnostic imaging should be performed, and a definitive diagnosis should be made quickly. Anticancer treatment should be planned multidisciplinary. Decompression surgery should be discussed for patients with severe neurological deficits. Childhood cancers are chemosensitive; if possible, treatment should be initiated with chemotherapy to avoid neurological sequelae.

Unraveling the Mystery: Next Generation Sequencing Sheds Light on Neuroblastoma Pathogenesis and Targeted Therapies.

BACKGROUND: There is considerable interest in the molecular evaluation of solid tumors in pediatric cases. Although clinical trials are in progress for targeted therapies against neuroblastoma (NB), novel therapeutic strategies are needed for high-risk cases that are resistant to therapy. The aim of the present study was to document the specific gene mutations related to targeted therapy in relapsed or refractory NB patients by using next generation sequencing (NGS). METHODS: The study included 57 NB patients from amongst 1965 neuroblastic cases in Turkey who experienced a recurrence after multi-model therapy. The cases were diagnosed, risk-stratified, and treated according to the classification system from the International Neuroblastoma Risk Group. Single nucleotide variations in 60 genes were investigated using the Pillar Onco/Reveal Multicancer v4 panel and Pillar RNA fusion panel on the Illumina Miniseq platform. RESULTS: ERBB2 I655V was the most frequent mutation and was found in 39.65% of cases. Anaplastic Lymphoma Kinase (ALK) mutations (F1174L, R1275Q, and rare mutations in the tyrosine kinase domain) were detected in 29.3% of cases. Fusion mutations in NTRK1, NTRK3, ROS1, RET, FGFR3, ALK and BRAF were observed in 19.6% of cases. CONCLUSIONS: This study presents valuable mutation data for relapsed and refractory NB patients. The high frequency of the ERBB2 I655V mutation may allow further exploration of this mutation as a potential therapeutic target. Rare BRAF mutations may also provide opportunities for targeted therapy. The role of ABL1 mutations in NB should also be explored further.

Dinutuximab beta plus conventional chemotherapy for relapsed/refractory high-risk neuroblastoma: A single-center experience.

Background: Relapsed/refractory high-risk neuroblastoma has a dismal prognosis. Anti-GD2-mediated chemo-immunotherapy has a notable anti-tumor activity in patients with relapsed/refractory high-risk neuroblastoma. The purpose of this study was to analyze the efficacy and safety of the combination of immunotherapy with dinutuximab beta (DB) and chemotherapy in patients with relapsed/refractory high-risk neuroblastoma. Methods: All patients received the Turkish Pediatric Oncology Group NB 2009 national protocol for HR-NB treatment at the time of diagnosis. Salvage treatments were administered after progression or relapse. The patients who could not achieve remission in primary or metastatic sites were included in the study. The most common chemotherapy scheme was irinotecan and temozolomide. DB was administered intravenously for 10 days through continuous infusion with 10 mg/m2 per day. The patients received 2 to 14 successive cycles with duration of 28 days each. Disease assessment was performed after cycles 2, 4, and 6 and every 2 to 3 cycles thereafter. Results: Between January 2020 and March 2022, nineteen patients received a total of 125 cycles of DB and chemotherapy. Objective responses were achieved in 12/19 (63%) patients, including complete remission in 6/19 and partial response in 6/19. Stable disease was observed in two patients. The remaining five patients developed bone/bone marrow and soft tissue progression after 2-4 cycles of treatment. The most common Grade ≥3 toxicities were leukopenia, thrombocytopenia, hypertransaminasemia, fever, rash/itching and capillary leak syndrome, respectively. Conclusion: Our study results suggest that DB-based chemo-immunotherapy seems to be suitable with encouraging response rates in patients with relapsed/refractory high-risk neuroblastoma.

The Serum Prolidase Enzyme Activity as a Biomarker for Evaluation of the Subclinical Vascular Damage in Children with Epilepsy.

BACKGROUD: Epilepsy is a chronic medical condition requiring long term or even lifelong therapy. Various researches have shown that epilepsy patients have vascular risk factors such as abnormal lipids, insulin, elevated oxidative stress, chronic inflammation, and subclinical atherosclerosis. OBJECTIVES: The purpose of the present study was to determine serum prolidase enzyme activity as a biomarker in children taking antiepileptic drug treatment through comparison with control cases. MATERIALS AND METHODS: The present study group consists of 61 children (20 females, 41 males) with epilepsy and a control group was formed of 32 healthy individuals (14 females, 18 males). Aspectrophotometric method was used to measure serum prolidase enzyme activity. RESULTS: The epilepsy group demonstrated statistically significantly higher prolidase enzyme activity values when compared with the control group (P = 0.003). It was measured that the serum TOS and OSI values were significantly elevated in patients with epilepsy compared to controls (P < 0.001). However, serum TAS values were significantly lower in the epilepsy group than in the control group (P = 0.032). CONCLUSIONS: These results supported that epileptic patients taking the antiepileptic treatment had increased serum prolidase enzyme activity, suggesting that it may show an increased risk of subclinical vascular damage related to both chronic inflammation and fibrotic process associated with degenerated collagen turnover. Therefore, serum prolidase enzyme activity could be considered a useful biomarker for evaluation of the subclinical vascular damage in children with epilepsy on some antiepileptic drugs.

Radiological staging in neuroblastoma: computed tomography or magnetic resonance imaging?

PURPOSE: To compare the effectiveness of computed tomography (CT) and magnetic resonance imaging (MRI) in the staging of neuroblastomas according to the International Neuroblastoma Risk Group Staging System (INRGSS). MATERIAL AND METHODS: In this single-centre retrospective study we identified a total of 20 patients under the age of 18 years, who were admitted to our hospital with neuroblastoma between January 2005 and May 2018, and who had both CT and MRI examination. The INRGSS stages of tumours were evaluated by CT scan and MRI. Then, stages of tumours were described according to the INRGSS for CT and MRI, separately. The Spearman rank correlation test was used for statistical analysis. The p-value < 0.05 was considered as statistically significant. RESULTS: The median age was 11 months, and the age range was one month to nine years. In our results; both MRI and CT were significant in the determination of radiological staging of NBL, p < 0.001 and p = 0.002, respectively. MRI was superior to CT in radiological staging. MRI was also superior for the detection of intraspinal extension, involvement of multiple body compartments, metastatic disease, and bone marrow infiltration. CT was more useful to consider the relationship between tumours and vascular structures. CONCLUSIONS: MRI and CT have high diagnostic accuracy rates in the staging of pre-treatment neuroblastomas. MRI is important in pre-treatment evaluation of neuroblastomas because of the higher detection of metastases as well as the lack of ionising radiation.

The association between serum vitamin B12 deficiency and tension-type headache in Turkish children.

This study aimed to determine the relationship between serum vitamin B12 level and tension-type headache. The study groups consisted of 75 patients (40 females, 35 males) with headache and a control group of 49 healthy children (25 females, 24 males). Serum vitamin B12 level < 200 pg/ml was defined as deficient, and < 160 pg/ml as severely deficient. The serum vitamin B12 level was measured by the electrochemiluminescence (ECLIA) method. The serum vitamin B12 levels in the headache and control groups were 273.01 ± 76.77 and 316.22 ± 74.53 pg/ml, with the difference determined as statistically significant (p = 0.003). In the case group, 18/75 patients (24%) had a serum vitamin B12 level below the normal of 200 pg/ml, and in the control group 4/49 (8%) patients were also below the normal range (p = 0.021). The serum vitamin B12 level in the children with tension-type headache was significantly lower than that in the control group. From the results of the study, it was concluded that there may be an association between vitamin B12 level and tension-type headache. However, further clinical studies are needed.

Comparison of Cisplatin with Lipoplatin in Terms of Ototoxicity.

OBJECTIVE: Cisplatin (CDDP) is an anti-neoplastic agent that has been used in treatments of both pediatric and adult cancers. It has many side effects, such as ototoxicity, nephrotoxicity, and neurotoxicity. Lipoplatin (LIPO) is a nanomolecule with 110 nm diameter and composed of lipids and CDDP. In this study, we aimed to compare the toxic effects of LIPO with CDDP in the cochlear cells with anti-tumoral doses determined in neuroblastoma cells. MATERIALS AND METHODS: House Ear Institute Organ Corti 1 (HEI-OC1), MYC-N amplified KELLY, and MYC-N non-amplified SH-SY5Y human neuroblastoma cells were used in this study. Firstly, anti-tumoral lethal dose 50 (LD50) of LIPO and CDDP were determined using the WST-1 assay in both neuroblastoma cells. Then anti-tumoral doses of CDDP and LIPO were applied on HEI-OC1 cells for evaluating the toxic effects. The apoptotic cell death was measured using flow cytometric analysis of annexin-V/7-amino-actinomycin (7-AAD) and cell cycle tests. RESULTS: LIPO or CDDP inhibited cell viability in a dose- and time-dependent manner in both neuroblastoma and HEI-OC1 cells. LD50 values were selected as 20 mM for CDDP and 750 mM for LIPO in neuroblastoma cells. After the 48-hour incubation, KELLY cells treated with 20 mM CDDP and 750 mM LIPO had a 53% viability; SH-SY5Y cells treated 20 mM CDDP and 750 mM LIPO had a 45% and 58% viability, respectively; and HEI-OC1 cells treated with 20 mM CDDP and 750 mM LIPO had a 65% and 82% viability, respectively. CONCLUSION: LIPO showed less toxic effects in the HEI-OC1 cells compared to CDDP at anti-tumoral doses.

Treatment of high-risk neuroblastoma: National protocol results of the Turkish Pediatric Oncology Group.

BACKGROUND: The national protocol aimed to improve the outcome of the high risk neuroblastoma patients by high-dose chemotherapy and stem cell rescue with intensive multimodal therapy. MATERIALS AND METHODS: After the 6 induction chemotherapy cycles, patients without disease progression were nonrandomly (by physicians' and/or parent's choices) allocated into two treatment arms, which were designed to continue the conventional chemotherapy (CCT), or myeloablative therapy with autologous stem cell rescue (ASCR). RESULTS: Fifty-six percent (272 patients) of patients was evaluated as high risk. Response rate to induction chemotherapy was 71%. Overall event-free survival (EFS) and overall survival (OS) at 5 years were 28% and 36%, respectively. "As treated" analysis documented postinduction EFS of 41% in CCT arm (n = 138) and 29% in ASCR group (n = 47) (P = 0.042); whereas, OS was 45% and 39%, respectively (P = 0.05). Thirty-one patients (11%) died of treatment-related complications. CONCLUSION: Survival rates of high-risk neuroblastoma have improved in Turkey. Myeloablative chemotherapy with ASCR has not augmented the therapeutic end point in our country's circumstances. The adequate supportive care and the higher patients' compliance are attained, the better survival rates might be obtained in high-risk neuroblastoma patients received myeloablative chemotherapy and ASCR.

Angiomatoid fibrous histiocytoma: case report and review of the literature.

Angiomatoid fibrous histiocytoma is a rare soft tissue tumor of uncertain differentiation and low metastatic potential, which occurs predominantly in children and young adults. It occurs mostly within the extremities, trunk, head and neck. It can be associated with systemic manifestations such as anemia, pyrexia and malaise. Its morphology is distinct, with an outer shell of lymphoid tissue, sheets of dendritic-like tumor cells with bland nuclei and blood-filled cystic cavities. Herein, we present a case of angiomatoid fibrous histiocytoma with systemic symptoms before any mass was clinically detectable, arising in the scalp of a 10-year-old girl.

Apoptotic Effects of Sanguinarine on the Organ of Corti 1 Cells: Comparison with Cisplatin.

OBJECTIVE: Sanguinarine is an alkaloid obtained from the root of Sanguinaria canadensis and other plants from the Papaveraceae family and is well known to possess a broad range of biological functions, such as antimicrobial, antifungal, anti-inflammatory, and antineoplastic activities. We aimed to specify the in vitro effect of sanguinarine on the House Ear Institute-Organ of Corti 1 (HEI-OC1) cells and to compare this effect with the ototoxic effect of cisplatin (CDDP). MATERIALS AND METHODS: We performed cell proliferation assay for determining the in vitro effect of sanguinarine alone and compared it with the effect of cisplatin. Flow cytometry annexin-V apoptosis detection was performed. RESULTS: We found that sanguinarine and CDDP inhibited the cell growth in a dose-dependant manner in HEI-OC1 cells after 24 h of incubation. In sanguinarine-treated group, apoptosis was 6.6%, necrosis was 26.7%, and the cell viability was 66.7%. Further, in CDDP-treated group, apoptosis was 5.6%, necrosis was 45.4%, and the cell viability was 48.7%. According to the annexin-V apoptosis detection results, we found that sanguinarine caused 3.9% apoptosis and 1.3% necrosis, while CDDP caused 2.9% apoptosis and 20% necrosis on HEI-OC1 cells. CONCLUSION: Our findings suggested that lower doses of sanguinarine are promising antineoplastic agents, which did not indicate any toxic effect on HEI-OC1 cells. Application of these data to clinical practice requires further support by in vivo studies.

Promoting effects of sanguinarine on apoptotic gene expression in human neuroblastoma cells.

Neuroblastoma is the most common extracranial solid tumor in children. Approximately half of the affected patients are diagnosed with high-risk poor prognosis disease, and novel therapies are needed. Sanguinarine is a benzophenanthridine alkaloid which has anti-microbial, anti-oxidant and anti-inflammatory properties. The aim of this study is whether sanguinarine has in vitro apoptotic effects and which apoptotic genes might be affected in the human neuroblastoma cell lines SH-SY5Y (N-myc negative), Kelly (N-myc positive, ALK positive), and SK- N-BE(2). Cell viability was analysed with WST-1 and apoptotic cell death rates were determined using TUNEL. After RNA isolation and cDNA conversion, expression of 84 custom array genes of apoptosis was determined. Sanguinarine caused cell death in a dose dependent manner in all neuroblastoma cell lines except SK-N-BE(2) with rates of 18% in SH-SY5Y and 21% in Kelly human neuroblastoma cells. Cisplatin caused similar apoptotic cell death rates of 16% in SH-SY5Y and 23% in Kelly cells and sanguinarine-cisplatin combinations caused the same rates (18% and 20%). Sanguinarine treatment did not affect apoptototic gene expression but decreased levels of anti-apoptotic genes NOL3 and BCL2L2 in SH-SY5Y cells. Caspase and TNF related gene expression was affected by the sanguinarine-cisplatin combination in SH-SY5Y cells. The expression of regulation of apoptotic genes were increased with sanguinarine treatment in Kelly cells. From these results, we conclude that sanguinarine is a candidate agent against neuroblastoma.

Vasoactive intestinal peptide releasing tumor which caused to chronic watery diarrhea and hypokalemia.

Watery diarrhea, hypokalemia and achlorhydria syndrome is a rare cause of chronic secretory diarrhea arising from a vasoactive intestinal peptide releasing tumor. In this article, a 15-month old female patient with watery diarrhea and abdominal distension which lasting four months is presented. In different centers no diagnosis could be made although investigations. The patient was diagnosed with vasoactive intestinal peptide releasing ganglioneuroblastoma localized in the right surrenal gland.

The time to diagnosis in childhood lymphomas and other solid tumors.

BACKGROUND: There are few reports from developing countries on the factors that influence the time to diagnosis (TD) in childhood cancer. The purpose of this study was to investigate the determinants of the TD in Turkish cancer patients. PROCEDURE: A retrospective analysis was performed on 329 children diagnosed with cancer, excluding leukemia. The TD, including parent/patient time and physician time, was defined as the interval between the onset of symptoms and the final diagnosis. RESULTS: The median times for parent/patient, physician, and TD were 3, 28, and 53 days, respectively. For patient in the 1-9 years age group, physician time and TD were significantly shorter than in infants and those over 10 years. The longest median TD was recorded for children with germ cell tumors and retinoblastoma; the shortest was in children with renal tumors. When the first point of contact was a pediatrician, a private hospital or physician's office, a governmental educational hospital or a university hospital physician time was short. The longest TD was noted in patients who first contacted a non-pediatric specialist. The most significant predictors of parent/patient, physician time, and TD were metastases at diagnosis, first medical center, and first health professional contacted, respectively. CONCLUSIONS: The TD for childhood lymphomas and solid tumors was related to patient age, tumor type and location, the presence of distance metastases, first health professional, and center contacted. All physicians, especially other specialists seeing pediatric patients, need to be further sensitized to the signs and symptoms of childhood cancer.

Soft tissue sarcomas and central nervous system tumors in children with neurofibromatosis type 1.

OBJECTS: We aim to evaluate the characteristics of pediatric patients with neurofibromatosis type 1 (NF1) who developed soft tissue sarcomas (STSs) and central nervous system (CNS) tumors that have been followed up in our center. MATERIALS AND METHODS: Medical records of children with NF1 were retrospectively analyzed. RESULTS: There were 78 patients who met at least two diagnostic criteria for NF1. The median age of patients was 10 years (0.5-18), and M/F ratio was 1.3. The prevalance of the optic glioma was 11.5% (n = 9), and one patient with optic glioma also had cystic astrocytoma, one patient had brain stem tumor, and one patient had a CNS tumor (without histopathologic diagnosis). Seven of nine children were ≥ 7 years old at the time of the diagnosis of optic glioma. Visual impairment developed in four patients, and two of them were treated with radiotherapy solely on the basis of evidence of clinical and radiological progression of the tumors. Four patients developed STSs. Two of them had malignant peripheral nerve sheath tumors (MPNST), and the remaining two had bladder rhabdomyosarcoma. Three of the four patients with STSs died with progressive disease. CONCLUSION: The clinical course of malignancy in NF1 is often different from that of similar tumor types in the general population. Careful follow-up in patients with NF1 is required to enable the early diagnosis of malignancies, and the developments of new targeted therapies are needed for improvement of the outcome for patients of this group, especially with MPNST.

Involuntary movement in infants during vitamin B12 treatment.

Megaloblastic anemia is rare in infants and is generally due to vitamin B12 (cobalamin) deficiency in the mother. Neurologic symptoms of vitamin B12 deficiency include irritability, failure to thrive, hypotonia, and developmental regression/delay. Herein we present 2 infants with vitamin B12 that developed movement disorder 5 d after initiation of vitamin B12 treatment. Symptoms included tremor and myoclonus, involving in particular the face, tongue, and hands. Clinical findings in infants associated with vitamin B12 deficiency vary, and temporary involuntary movement can be observed during vitamin B12 therapy.

Challenges of radiological assessment in an infant with giant calcified hepatoblastoma.

Hepatoblastoma is a rare neoplasm of all pediatric cancers. The goal of treatment is to remove the tumor completely because cure without complete resection is extremely unusual. Accurate assessment of tumor resectability following preoperative chemotherapy is of crucial importance. It is sometimes difficult, especially when the tumor is as large and calcified as in the described case. Detailed radiological imaging such as computed tomography angiography or magnetic resonance angiography is the key for selecting the proper treatment method in hepatoblastoma during the preoperative period. In this article, we report a successfully treated giant calcified hepatoblastoma despite radiological assessment complexity.

An extremely rare cause of generalized lymphadenopathy in children: Kimura's disease.

Kimura's disease, characterized by a triad of painless subcutaneous masses in the head and neck, prominent eosinophilia and markedly elevated immunoglobulin E levels, is an uncommon idiopathic, chronic inflammatory disease that usually affects young and middle-aged Asian males. Kimura's disease is known usually as a localized process and is an extremely rare cause of generalized lymphadenopathy in children. We report an eight-year-old Turkish boy with Kimura's disease who presented with generalized lymphadenopathy masquerading as malignant lymphoma.

Atypical teratoid/rhabdoid tumor in an infant conceived by in vitro fertilization.

BACKGROUND: Atypical teratoid/rhabdoid tumor (ATsRT) is a rare tumor and extremely aggressive embryonal neoplasm of the central nervous system. Brain tumors in infant are suggestive of some oncogenic prenatal factors. CASE PRESENTATION: We report on a case of ATRT in a 4-month-old infant conceived by in vitro fertilization (IVF). Some previous reports have raised a question about the possible relation between IVF and childhood cancer, particularly embryonal tumors. CONCLUSION: Report of such cases may provide some evidence to identify if there is a real association between congenital tumors and IVF.