Surgical Management of Brain Tumors in Infants Under One Year of Age.

AIM: To comprehensively analyze clinical presentation, diagnosis, and management approaches of brain tumors in infants under one year of age. MATERIAL AND METHODS: We conducted a retrospective analysis of clinical data retrieved from medical records of infants who underwent surgical treatment for intracranial mass lesions at our institution from January 2006 to December 2016. The data encompassed parameters such as age at diagnosis, symptoms, tumor location, histology, surgical procedures, adjuvant treatment, and survival outcomes. Cases involving dermoid, epidermoid cysts, and other skull-based lesions were excluded from the analysis. RESULTS: Our analysis identified twenty-three cases of brain tumors diagnosed within the first year of life, comprising 14 boys and 9 girls. The median age at diagnosis was 8.2 months, and the most common presenting symptoms were nausea and vomiting, as well as head circumference abnormalities. Successful gross total resection was achieved in 75.8% of patients, with choroid plexus papilloma being the most frequently encountered histopathological diagnosis. Eight patients received adjuvant chemotherapy, while one patient underwent salvage radiotherapy. CONCLUSION: The treatment of brain tumors in infants during their first year of life presents significant challenges. The affected patients exhibit diverse tumor pathologies occurring at various locations within the brain. Further research is warranted to establish optimal treatment options for this specific population.

Nivolumab for relapsed or refractory Hodgkin lymphoma: real-life experience.

Classical Hodgkin lymphoma (cHL) is considered a curable disease; however, in approximately one-third of the responding patients, the disease relapses following completion of therapy. One of the drugs that have been approved for the treatment of relapsed/refractory cHL is nivolumab, an immune check point inhibitor that shows its effects by blocking the programmed death 1 (PD-1) receptor. In this study, we present a retrospective "real-life" analysis of the usage of nivolumab in patients with relapsed/refractory cHL that have joined the named patient program (NPP) for nivolumab, reflecting 4 years of experience in the treatment of relapsed/refractory cHL. We present a retrospective analysis of 87 patients (median age, 30) that participated in the NPP in 24 different centers, who had relapsed/refractory cHL and were consequently treated with nivolumab. The median follow-up was 29 months, and the median number of previous treatments was 5 (2-11). In this study, the best overall response rate was 70% (CR, 36%; PR, 34%). Twenty-eight of the responding patients underwent subsequent stem cell transplantation (SCT). Among 15 patients receiving allogeneic stem cell transplantation, 9 patients underwent transplantation with objective response, of which 8 of them are currently alive with ongoing response. At the time of analysis, 23 patients remained on nivolumab treatment and the rest discontinued therapy. The main reason for discontinuing nivolumab was disease progression (n = 23). The safety profile was acceptable, with only nine patients requiring cessation of nivolumab due to serious adverse events. The 24-month progression-free and overall survival rates were 58.5% (95% CI, 0.47-0.68) and 78.7% (95% CI, 0.68-0.86), respectively. Eighteen patients died during the follow-up and only one of these was regarded to be treatment-related. With its efficacy and its safety profile, PD-1 blockers became an important treatment option in the heavily pretreated cHL patients.

Late effects in patients with sacrococcygeal teratoma: A single center series.

INTRODUCTION: The aim of this study is to evaluate late side effects that affect quality of life in children with sacrococcygeal teratoma (SCT). PATIENTS AND METHODS: The patients with SCT were evaluated retrospectively. The data were expressed by percentage and the subgroups were compared statistically. RESULTS: A total of 40 children with SCT were identified with median age 12 days (range: 1 day-14.6 years), 27 of whom were analyzed in this study with urodynamic data available for 24 and anal manometric evaluations for 20. Chronic constipation with need for laxative was reported in (7/27) 25.9%, fecal incontinence was present in (1/27) 3.7%, and urodynamic abnormalities were reported in (16/24) 66%. Among those with urodynamic abnormalities, low bladder capacity, dyssyergia and neurogenic bladder were observed in (21/24) 87.5% and anticholinergic treatment was applied. Urinary incontinence was present in (2/27) 7%, with clean intermittent catheterization utilized in (7/27) 25.9%. While defecation was observed more in the patients with Altman types II, III, and IV, micturation problems were observed more in the patients with Altman types II and IV. It was found that urodynamic dysfunctions were more frequent in the patients with increased number of operations. DISCUSSION: Although the rate of symptomatic patients was low, abnormalities determined by radiological and urodynamic evaluations were high.

Congenital Factor Deficiencies in Children: A Report of a Single-Center Experience.

Congenital factor deficiencies (CFDs) refer to inherited deficiency of coagulation factors in the blood. A total of 481 patients with CFDs, who were diagnosed and followed at our Pediatric Hematology and Oncology Clinic between 1990 and 2015, were retrospectively evaluated. Of the 481 cases, 134 (27.8%) were hemophilia A, 38 (7.9%) were hemophilia B, 57 (11.8%) were von Willebrand disease (vWD), and 252 (52.3%) were rare bleeding disorders (RBDs). The median age of the patients at the time of diagnosis and at the time of the study was 4.1 years (range: 2 months to 20.4 years) and 13.4 years (range: 7 months to 31.3 years), respectively. The median duration of the follow-up time was 6.8 years (range: 2.5 months to 24.8 years). One hundred nineteen (47.2%) of 252 patients with RBDs were asymptomatic, 49 (41.1%) of whom diagnosed by family histories, 65 (54.6%) through preoperative laboratory studies, and 5 (4.2%) after prolonged bleeding during surgeries. Consanguinity rate for the RBDs was 47.2%. Prophylactic treatment was initiated in 80 patients, 58 of whom were hemophilia A, 7 were hemophilia B, 13 were RBDs, and 2 were vWD. Significant advances have been achieved during the past 2 decades in the treatment of patients with CFDs, particularly in patients with hemophilias. The rarity and clinical heterogeneity of RBDs lead to significant diagnostic challenges and improper management. In this regard, multinational collaborative efforts are needed with the hope that can improve the management of patients with RBDs.

Urothelial Carcinoma of the Bladder in Pediatric Patient: Four Case Series and Review of the Literature

Background: Urothelial carcinoma of the bladder is a rare condition in children, and most cases in this age group are noninvasive and low-grade. However, no follow-up protocol has been defined for this patient group. The objective of this study was to draw attention to bladder tumors in children and focus on the current recommendations for postoperative follow-up along with a case study of four patients. Case Report: Four patients aged <18 years with urothelial carcinoma who were treated in our clinics between 2001 and 2015 were retrospectively evaluated. The results were compared with those of published pediatric case series in the literature. No abnormalities were found in the patients' physical examinations and laboratory analyses, except hematuria (microscopic or macroscopic). Ultrasonography was used in all the patients to detect lesions in the bladder. Surgical resections were performed endoscopically, except in one patient. Histopathological evaluations revealed low-grade superficial urothelial carcinoma. No recurrence or complication was observed for all patients. Conclusion: Although rarely encountered during childhood, urothelial carcinoma should be considered as a differential diagnosis in pediatric patients with hematuria.

A prospective follow-up of quality of life, depression, and anxiety in children with lymphoma and solid tumors

Background/aim: The aim of this study was the determination and prospective follow-up of quality of life, depression, and anxiety in pediatric patients with cancer under chemotherapy, as well as the evaluation of related factors. Materials and methods: Fifty newly diagnosed pediatric cancer patients and their parents were prospectively monitored before, during, and after therapy, and tests were used. Results: Significantly lower quality of life scores were recorded during treatment, in the group with CNS tumors, in the group receiving chemotherapy plus radiotherapy plus surgery, in the inpatient-only treatment group, in the group receiving treatment for longer than 6 months, and in the group of patients whose diagnosis was delayed for more than 3 months. Total quality of life scores for children and their parents were 82.95 ± 14.59 vs. 83.61 ± 14.60 before, 54.69 ± 16.51 vs. 55.78 ± 16.05 during, and 83.88 ± 12.44 vs. 84.19 ± 13.22 at the end of treatment (P < 0.05). Anxiety and depression scores were significantly higher during treatment, in patients whose diagnoses were delayed for more than 3 months, and among inpatients. Conclusion: The quality of life of a majority of our patients was severely affected, and depression and anxiety were more frequently seen especially during treatment.

Leptomeningeal dissemination and vertebral bone involvement in a child with pilocytic astrocytoma.

In low-grade glioma, metastasis is rarely seen. Few cases of leptomeningeal dissemination have been reported in children. Vertebral bone metastasis has not been reported so far. Herein is described the case of a pediatric patient with the diagnosis of pilocytic astrocytoma, and leptomeningeal dissemination detected at the time of diagnosis, who then received radiotherapy and chemotherapy upon development of vertebral bone metastasis during treatment.

Evaluation of late effects of postoperative radiotherapy in patients with medulloblastoma.

We aimed to evaluate long-term toxicity in children with medulloblastoma treated with postoperative radiotherapy (RT). This study included 21 patients aged 4-16 who had been diagnosed with medulloblastoma. All of the patients in the study received postoperative craniospinal RT. Postoperative RT followed by chemotherapy was the treatment protocol. A total of 13 patients (62%) received chemotherapy concurrently with RT. Overall survival was 50 months (range, 1-169 months) and disease-free survival was 39 months (range, 4-171 months). In the data analysis, the heights of 11 patients (91.6%) were found to be below 50% on the height curve, and 8 (66.6%) patients had weights below 50% on the weight curve. Mean sitting height was 72.58 ± 6.33 cm, and this was statistically correlated with parameters such as LH level (p=0.037), testosterone level (p=0.020), height (p=0.002), weight (p=0.033) and age at diagnosis (p=0.002). Radiation therapy for medulloblastoma seems to have a late toxic effect on long-term survivors. With the improving survival rate of medulloblastoma patients, RT doses should be as low as possible without sacrificing efficacy.

Successful treatment of multiresistant Achromobacter xylosoxidans bacteremia in a child with acute myeloid leukemia.

Achromobacter xylosoxidans is an aerobic gram-negative bacillus and important cause of bacteremia in immunocompromised patients. We describe a leukemia pediatric patient with severe neutropenia who developed bacteremia with A xylosoxidans resistant to multiple antibiotics, and treated the patient with tigecycline and piperacillin-tazobactam in addition to supportive medications.

Adrenomedullin--A New Marker in Febrile Neutropenia: Comparison With CRP and Procalcitonin.

In this study, we aimed to determine serum adrenomedullin levels and compare them with levels of C-reactive protein (CRP) and procalcitonin (PCT). Cancer patients aged 0-18 years who experienced febrile neutropenia attacks were included in the study. Adrenomedullin, CRP, and PCT were analyzed at admission, day 3, and days 7-10 later. Fifty episodes of febrile neutropenia that developed in 37 patients were analyzed in this study. The mean age of the patients was 7.5 ± 4.7 (1-18) years. The patients had leukemia (73%), solid tumors (19%), and lymphoma (8%). The percentages of the patients in the clinically documented infection (CDI), fever of unknown origin (FUO), sepsis, and microbiological documented infection (MDI) categories were 34%, 34%, 20%, and 12%, respectively. During the study period, four patients were lost. In the MDI group, adrenomedullin levels on day 3 were significantly higher than those in the CDI and FUO groups. PCT levels were significantly higher in the sepsis group than those in the CDI group at admission, day 3, and days 7-10. In the sepsis group, PCT levels on days 7-10 days were significantly higher than those in the sepsis group. PCT values from the deceased patients on days 7-10 were significantly higher than those from patients who survived. CRP levels did not differ significantly among the febrile neutropenia groups. First, in our study, adrenomedullin was used as a biomarker in the febrile neutropenia episodes of children with cancer. Among adrenomedullin, CRP, and PCT, procalcitonin demonstrates the highest correlation with the severity of infection.

Catheter-associated bloodstream infections in pediatric hematology-oncology patients.

Catheter-associated bloodstream infections (CABSIs) are common complications encountered with cancer treatment. The aims of this study were to analyze the factors associated with recurrent infection and catheter removal in pediatric hematology-oncology patients. All cases of CABSIs in patients attending the Department of Pediatric Hematology-Oncology between January 2008 and December 2010 were reviewed. A total of 44 episodes of CABSIs, including multiple episodes involving the same catheter, were identified in 31 children with cancer. The overall CABSIs rate was 7.4 infections per 1000 central venous catheter (CVC) days. The most frequent organism isolated was coagulase-negative Staphylococcus (CONS). The CVC was removed in nine (20.4%) episodes. We found that hypotension, persistent bacteremia, Candida infection, exit-side infection, neutropenia, and prolonged duration of neutropenia were the factors for catheter removal. There were 23 (52.2%) episodes of recurrence or reinfection. Mortality rate was found to be 9.6% in children with CABSIs. In this study, we found that CABSIs rate was 7.4 infections per 1000 catheter-days. CABSIs rates in our hematology-oncology patients are comparable to prior reports. Because CONS is the most common isolated microorganism in CABSIs, vancomycin can be considered part of the initial empirical regimen.

Randomized comparison of piperacillin-tazobactam plus amikacin versus cefoperazone-sulbactam plus amikacin for management of febrile neutropenia in children with lymphoma and solid tumors.

The objective of this study was to compare the effectiveness of piperacillin-tazobactam (PIP/TAZO) plus amikacin (AMK) (PIP/TAZO+AMK) versus cefoperazone-sulbactam (CS) plus AMK (CS+AMK) for the treatment of febrile neutropenia (FN) in children with cancer. The study was designed prospectively and randomized in 0- to 18-year-old children with lymphoma or solid tumor who were hospitalized with FN diagnosis. Consecutively randomized patients received either PIP/TAZO 360 mg/kg/day in 4 doses plus AMK 15 mg/kg/day in 3 doses or CS 100 mg/kg/day in 3 doses plus AMK 15 mg/kg/day in 3 doses intravenously. Treatment modification was defined as any change in the initial empirical antibiotic therapy. A total of 116 FN episodes were managed in 46 patients (26 boys and 20 girls) with a median age of 6.5 years (range .8-17.0) during the study period. Success rates without modification of therapy were 47.5% and 52.6% in PIP/TAZO+AMK group and CS+AMK group, respectively (P >.05). No statistical difference was found between treatment groups in terms of durations of neutropenia, fever, and hospitalization. The overall success rate in all groups was 97.4%. No major side effect was observed in either group during the course of the study. Our study is the first to compare the effectiveness of PIP/TAZO+AMK and CS+AMK therapies. Both combinations were effective and safe as empirical therapy for febrile neutropenic patients.

Use of complementary and alternative medicine in children with cancer: effect on survival.

The objective of the present study was to determine the type, frequency, the reason why complementary and alternative medicine (CAM) treatments are used, the factors related with their use, and the effects of CAM usage on long-term survival. Families of a total of 120 children with cancer between 0-18 years of age, including 50 (41.7%) girls and 70 (58.3%) boys, participated in our study. The authors found that 88 patients (73.3%) used at least one CAM method, the most common (95.5%) of which was biologically based therapies. Most frequently used biologically based therapies were dietary supplements and herbal products. The most commonly used dietary supplement or herbal product was honey (43.2%) or stinging nettle (43.2%), respectively. We found that patients used such CAM methods as complementary to, but not instead of, conventional therapy. Sixty-nine out of 88 patient families (78.4%) shared the CAM method they used with their physicians. No statistically significant relation was found between socioeconomic, sociodemographic, or other factors or items and CAM use. The mean follow-up period of the CAM users and nonusers groups was 79.4 ± 36.7 (21.3-217.9) and 90.9 ± 50.3 (27.4-193.7) months, respectively. Five-year survival rates for CAM users and nonusers were found as 81.5% and 86.5%, respectively (P > .05). In conclusion, families of children with cancer use complementary and alternative treatment frequently. They do not attempt to replace conventional treatment with CAM. Higher rates of CAM use was found in families with higher educational level. CAM usage did not affect the long-term survival.

Disseminated rhabdomyosarcoma presenting as hypercalcemia.

Hypercalcemia may be seen in children with malignancy. We report a 4 year old child with rhabdomyosarcoma that initially presented with signs of hypercalcemia and bone involvement.

Time-dependent alterations in growth and bone health parameters evaluated at different posttreatment periods in pediatric oncology patients.

Bone mineral density (BMD) and anthropometric measurements in pediatric cancer patients were evaluated and compared at early and late posttreatment periods. Sixty-six pediatric cancer patients who recovered completely following treatment longer than at least a 6-month period were included in the study. Patients were evaluated cross-sectionally and prospectively with regard to anthropometric measurements and BMD twice; the first being at a mean period of 2.62 ± 1.44 years and the second of 6.55 ± 1.71 years after the completion of treatment. Rates of osteoporosis and osteopenia at first or second evaluation were 25.8% and 39.4% or 10.6% and 19.7%, respectively. Mean BMD z-scores were (-1.26) ± 1.12 [(-4.3)-2.0] and (-0.48) ± 1.25 [(-3.30)-3.40] at first and second evaluations, respectively. BMD findings obtained at second evaluation revealed statistically significant recovery compared with those obtained at first evaluation (P = .001). BMD z-scores were significantly lower in patients who received, as opposed to those who did not receive, radiotherapy (RT) at both evaluations. Anthropometric parameters of patients such as height, weight, and body mass index (BMI) were increased at both evaluations compared with values obtained at diagnosis (P < .05). Height standard deviation score (SDS) decreased at first evaluation compared with that measured at diagnosis, whereas it increased at second evaluation. Conversely, weight SDS and BMI SDS increased (P < .05) at first evaluation compared with that measured at diagnosis, whereas they decreased at second evaluation. The authors conclude that early impairments in anthropometric measurements recover in the long term, whereas BMD is continually reduced in children who recovered from cancer.

Thyroid functions in long-term survivors of pediatric Hodgkin's lymphoma treated with chemotherapy and radiotherapy.

OBJECTIVE: Post-treatment endocrine disturbances are common in cancer patients who have received radiotherapy or chemotherapy. The objective of this study was to evaluate the thyroid functions of long-term survivors of pediatric Hodgkin's lymphoma treated with chemotherapy and radiotherapy. METHODS: Thyroid functions of 55 Hodgkin's lymphoma patients (M/F:2.05/1) in complete remission were evaluated retrospectively. RESULTS: The mean age of the patients at diagnosis was 10.35±4.09 (range: 2.83-17) years and the mean follow-up period was 5.54±3.68 (range: 0.92-13.92) years. All patients received chemotherapy; a total of 50 patients (90.9%) underwent radiotherapy, 42 (76.4%) of whom received neck/mantle radiotherapy. Thyroid function tests were abnormal in 14 (24.5%) patients and normal - in the remaining 41 (74.5%). A diagnosis of subclinical and overt hypothyroidism was made in 11 (78.6%) and 3 (21.4%) patients with abnormal thyroid function tests, respectively. Nearly one-fourth (21.4%) of all thyroid function disorders were detected in the first year of follow-up. A statistically significant correlation was found between the dose of mantle radiotherapy and thyroid function disorder (p=0.002). In addition, statistically significant correlations were established between thyroid examination or thyroid ultrasonography findings and thyroid functions (p <0.001 or p=0.006, respectively). CONCLUSIONS: Radiation-induced thyroid disorders may develop in pediatric Hodgkin's lymphoma patients in complete remission starting as early as the first year after treatment and are dose-dependent. Patients, particularly those who have been exposed to radiotherapy of the neck, must be followed up closely for occurrence of thyroid dysfunctions.

Recombinant human erythropoietin ß: the effect of weekly dosing on anemia, quality of life, and long-term outcomes in pediatric cancer patients.

Anemia, which is a common problem in cancer patients, has a negative effect on survival by decreasing the efficacy of chemotherapy and particularly of radiotherapy, as well as impairing the quality of life (QoL) of patients. Recombinant human erythropoietin (rHuEPO) decreases a patient's need for transfusions and increases their QoL. The aim of this study was to evaluate the effect of weekly single-dose EPO treatment on transfusion rates, QoL, and hemoglobin (Hb) levels. In addition, patients were followed up for a long period to assess the impact of EPO treatment on survival. The study was conducted from December 2001 to December 2002 in patients with newly diagnosed lymphoma or solid tumors using a prospective and controlled design. EPO-ß was given as a single dose of 450 U/kg once a week for 12 weeks. The study and control groups included 16 patients each. Hb levels measured in the study group at the 4th, 8th, and 12th weeks were significantly higher than the values recorded before the start of chemotherapy. In the control group, Hb levels post chemotherapy were significantly lower than values recorded prior to treatment. The increased Hb levels in the study group were significant at the 8th and 12th weeks of treatment compared to levels measured prior to treatment. In the control group, Hb levels at the 4th and 8th weeks were significantly lower than pretreatment levels. When the percent increase of Hb levels of the study and control groups with respect to treatment week was compared, the difference was statistically significant at the 4th, 8th, and 12th weeks. Although the increase on the performance scale within each group during treatment was significant in both the study and control groups, the increase was more marked in the study group. The percent increase on the performance scale with respect to week of treatment was higher in the study group than in the control group. In EPO treatment group, side effects were seen in 38% of patients, with 19% being local pain in the injection area, 13% local hyperemia, and 6% headache. The mean follow-up period of the study and control group was 7.03 ± 0.41 (6.0-7.41) and 7.46 ± 0.45 (6.58-7.83) years, respectively; no statistically significant difference existed between these figures. Overall survival at the end of 7 years of follow-up was 68.8% and 81.3% for the study and control groups, respectively. The use of EPO-ß in lymphoma and solid tumor patients on a once-weekly regimen (450 U/kg) was determined to be effective in increasing Hb levels, decreasing transfusion rates, and improving QoL. This regimen was safe, did not cause serious side effects, and can be recommended because of its high patient compliance and tolerability. An effect of EPO on prognosis was not evident. We could not have an explanation on the effect of EPO treatment on prognosis, as there were low number of patients and advanced-staged patients died earlier. Therefore, a larger number of patients are needed to clarify the effect of EPO treatment on prognosis.

Hyperuricemia and tumor lysis syndrome in children with non-Hodgkin's lymphoma and acute lymphoblastic leukemia.

OBJECTIVE: This study aimed to examine the incidence, clinical characteristics, and outcome of hyperuricemia and tumor lysis syndrome (TLS) in children with non-Hodgkin's lymphoma (NHL) and acute lymphoblastic leukemia (ALL). METHODS: This retrospective study included data from 327 patients (113 NHL and 214 ALL). RESULTS: Hyperuricemia occurred in 26.5% and 12.6% of the patients with NHL and ALL, respectively. The corresponding figures for TLS were 15.9% and 0.47% (p=0.001). All hyperuricemic NHL patients had advanced disease and renal involvement was present in 53%. All hyperuricemic ALL patients had a leukocyte count >50,000 mm3 at the time of diagnosis. Among the hyperuricemic NHL and ALL patients, 96.6% and 66.6% had LDH ≥500 UI/L, respectively. Treatment consisted of hydration and allopurinol; none of the patients received urate oxidase. Among the patients that developed TLS, 26.3% had laboratory TLS, 42.1% had grade I or II TLS, and 31.6% had grade III or IV TLS. Uric acid levels returned to normal after a mean period of 3.5±2.5 and 3.05±0.8 d in NHL and ALL groups, respectively. In all, 7% of the patients with hyperuricemia required hemodialysis. None of the patients died. CONCLUSION: In this series the factors associated with a high-risk for TLS were renal involvement in NHL and high leucocyte count in ALL. Management with allopurinol and hydration was effective in this group of patients with high tumor burden.

Reversible posterior leukoencephalopathy induced by cancer chemotherapy.

Reversible posterior leukoencephalopathy, defined by both clinical and neuroimaging findings, can affect children receiving chemotherapy. The syndrome is characterized by hypertension, alterations in mental status, seizures, hallucinations, and acute visual changes and is associated with abnormalities seen in magnetic resonance imaging of symmetric white matter lesions, especially in the parietal and occipital lobes. The etiology of reversible posterior leukoencephalopathy is as yet unknown. Presented here are four cases of reversible posterior leukoencephalopathy induced by chemotherapy, with a brief review of the literature and consideration of possible mechanisms. A diagnosis of reversible posterior leukoencephalopathy should be considered when patients receiving cancer chemotherapy suddenly develop hypertension followed by neurologic complications, especially if presenting with seizures.