Precursor B-cell Lymphoblastic Lymphoma in Children: Hacettepe Experience.

The purpose of the study was to review the clinical and pathologic characteristics and treatment results of children with precursor B-cell lymphoblastic lymphoma. Of 530 children diagnosed with non-Hodgkin lymphomas between 2000 and 2021, 39 (7.4%) were identified as having precursor B-cell lymphoblastic lymphoma. Clinical characteristics, pathologic, radiologic, laboratory data, treatments, responses, and overall outcomes were recorded from hospital files and analyzed. The median age of 39 patients (males/females, 23/16) was 8.3 years (range 1.3 to 16.1). The most common sites of involvement were the lymph nodes. At a median follow-up of 55.8 months, 14 patients (35%) had a recurrence of disease (11 stage IV, 3 stage III); 4 were in complete remission with salvage therapies, 9 died of progressive disease and one died due to febrile neutropenia. Five-year event-free survival and overall survival rates were 65.4% and 78.3% for all cases, respectively. Survival rates were higher in patients with a complete remission at the end of induction therapies. The survival rates were lower in our study compared with other studies, which could be explained by the high relapse rate and higher incidence of advanced-stage disease due to bone marrow involvement. We demonstrated a prognostic impact of treatment response at the end of the induction phase. Cases with a disease relapse have poor prognosis.

Assessment of nutritional status in children with cancer: Significance of arm anthropometry and serum visceral proteins.

BACKGROUND: Arm anthropometry is a better indicator of nutritional status in children with cancer. The value of serum albumin and prealbumin in nutritional assesment is debatable. We investigated the nutritional status of children with cancer and their serum albumin and prealbumin levels. PATIENTS AND METHODS: At diagnosis and following induction therapies, weight, height, body mass index (BMI), mid-upper arm circumference (MUAC), and triceps skin-fold thickness (TSFT) were measured; serum albumin and prealbumin levels were determined. Prevalences of malnutrition defined by anthropometric indices were calculated. Correlations of anthropometric indices with each other, with serum albumin/prealbumin levels, and clinicopathological parameters were analyzed. RESULTS: In 81 patients, median age was 7.5 years (males/females = 50/31), tumors were located mostly in the abdomen, and abdominal tumors were more common under 5 years. Prevalence of malnutrition according to weight for age, BMI, MUAC, TSFT z scores were 14.8%, 23.5%, 27.2%, 21%, respectively. Defined by combined BMI/MUAC/TSFT measurements, 33/81 cases (40.7%) had malnutrition (z scores < -1, 23 mild; z scores < -2, 10 moderate). Malnutrition was more prevalent under 5 years (P = .03), also in abdominal tumors (P = .03) and advanced disease (P < .001). Younger age and advanced disease were risk factors for malnutrition. At diagnosis, prevalences of low serum albumin and prealbumin levels were 7.4% and 54%, respectively. Cases with malnutrition had significantly lower survival rates. CONCLUSIONS: Nutritional status is assessed best by MUAC and TSFT measurements. Serum prealbumin levels can be used to identify patients at risk of undernutrition. Presence of malnutrition is a significant poor prognostic factor. All children with cancer should undergo nutritional evaluation and active nutritional support.

Primary Paraspinal and Spinal Epidural Non-Hodgkin Lymphoma in Childhood.

Primary paraspinal/spinal epidural lymphoma (PPSEL) is rare in childhood. Here, we retrospectively evaluated patients with PPSEL treated in our department. We also reviewed the cases reported in the literature. Fifteen of 1354 non-Hodgkin lymphoma cases diagnosed over a 38-year period were PPSEPL. There were 11 male individuals and 4 female individuals with a median age of 13 years. Most common symptoms were pain and limb weakness. Physical examination revealed spinal cord compression in 80% of patients. The most common tumor location was the lumbar region. Histopathologic subtypes were lymphoblastic lymphoma in 6 and Burkitt lymphom in 5 patients. Subtotal or near-total excision of the tumor with laminectomy was performed in 6 patients. Thirteen and 9 patients received chemotherapy and radiotherapy, respectively. Neurologic recovery was observed in 70% of patients. Seven patients were alive without disease at a median of 88 months. Overall and event-free survival rates were 61.7% and 50.1%, respectively. We reviewed clinical features, treatment, and outcome of 69 PPSEL cases reported in the literature. Neurologic recovery and long-term survival was achieved in 66.7% of them. Heterogeneity in diagnostic methods and treatment have made it difficult to establish the prognostic indicators for neurologic outcome and survival. Multicenter prospective studies with more cases are necessary to determine the prognostic factors.

Extraovarian juvenile granulosa cell tumor in a prepubertal child: novel location of a rare tumor.

Juvenile granulosa cell tumor (JGCT) is the most common type of sex cord stromal tumor arising from gonadal structures of children and young adults. We present a 3.5-year-old girl with JGCT located in retroperitoneum without ovarian involvement. Extragonadal occurrences of other sex cord stromal tumors have been rarely reported, but this is the first case of JGCT in an extragonadal location. We speculate the possible underlying mechanism of sex cord stromal tumor formation in extragonadal locations. Furthermore, clinical presentation, differential diagnosis and management of this tumor in childhood are discussed.

Primary gastric lymphoma: A report of 16 pediatric cases treated at a single institute and review of the literature.

Gastrointestinal tract is the most common extranodal site for childhood non-Hodgkin lymphomas (NHLs). However, primary gastric lymphoma (PGL) is very rare. We report our experience with PGL. Between 1972 and 2019, patients with PGL among 1696 NHL cases were evaluated retrospectively. Patient characteristics, treatments, and survival rates were recorded. We also reviewed the cases reported in literature. There were 16 PGL (11 males, five females) cases with a median age of 10 years. Most frequent complaints, similarly to the literature, were pain and vomiting. Hematemesis/melena and anemia were present in 20% of patients. Most common tumor location was antrum. Histopathological subtypes were Burkitt and non-Burkitt B-cell lymphoma in 43.75% and marginal zone lymphoma (MZL) in 6.25% of cases while mucosa-associated lymphoid tissue (MALT) and low-grade lymphomas constitute 15.3% of cases reported in the literature. In our series, Helicobacter pylori (H. pylori) was analyzed in only the case with MZL and found to be positive. However, H. pylori positivity was reported in 75% of the cases in the literature. H. pylori eradication, chemotherapy, and radiotherapy were applied in one, 14, and five patients. Subtotal gastrectomy with gastroduodenostomy/jejunostomy was performed in three patients. Gastrojejunostomy was done without tumor resection in two patients. Nine patients lived without disease for a median of 59 (12-252) months. Five-year EFS and OS were 69.6% and 64.3%, respectively. PGL constitutes 0.94% of our NHL cases. Interestingly, most of the cases in the literature were from Turkey. While adult PGL is mostly MALT lymphoma, most pediatric cases had high-grade histopathology. Although surgery and radiotherapy were applied earlier, chemotherapy alone is sufficient.

FAB LMB 96 Regimen for Newly Diagnosed Burkitt Lymphoma in Children: Single-center Experience.

BACKGROUND/OBJECTIVES: The outcome of Burkitt lymphoma has improved by over 90%. In this study, demographic characteristics and outcomes of 57 patients with Burkitt lymphoma treated with FAB LMB 96 regimen are presented. MATERIALS AND METHODS: Standard intensity arms were selected for all risk groups. Clinical characteristics, response to treatment, and outcome were evaluated. RESULTS: The median age of 48 boys and 9 girls was 8.2 years. There were 2 (3%), 41 (72%), and 14 (25%) patients in the low, intermediate, and high-risk groups, respectively. Patients were followed-up for a median of 50 months. The 5-year overall survival and event-free survival rates for the study group were 90.8% and 87.4%, respectively. Two patients in the low-risk group are still alive without evidence of disease for 17 and 57 months. The 5-year overall survival rates were 95% and 78% for intermediate and high-risk patients, and the 5-year event-free survival rates were 93% and 62%, respectively. At the end of induction, 58% of patients had complete response, and 42% (n=24) had residual tumors. A total of 16 of 24 patient biopsies showed no viable tumors. CONCLUSIONS: Our results confirm the previously published survival results of FAB LMB 96. The regimen is an effective regimen for mature B-cell non-Hodgkin lymphoma without radiotherapy or surgery even in central nervous system-positive patients. The most important prognostic factor is the complete response after induction chemotherapy. However, residual tumor at the end of consolidation might not always be a sign for unresponsive tumor. Tumoral residue should be radiologically well evaluated and biopsied if possible for viability before intensifying treatment.

Denosumab treatment in aneurysmal bone cyst: Evaluation of nine cases.

BACKGROUND: Aneurysmal bone cyst (ABC) is a benign bone tumor. Curettage and bone grafting is the common treatment. Here, we retrospectively evaluate nine patients treated with denosumab. PROCEDURE: Nine patients with ABC, mostly pelvic and vertebral, treated with denosumab were analyzed retrospectively. A 70 mg/m2 denosumab dose was used weekly in the first month, and then monthly. Clinical and radiological responses to treatment were evaluated. RESULTS: In all patients, clinical symptoms including pain and limping regressed completely within 3 months. Radiological evaluation revealed changes in lesion size and content. In six patients, overall volume reduction in the range of 18-82% was detected. Decreases in the size and number of cysts were detected in eight patients. In five patients, fat signal appeared on follow-up imaging. No major side effects were observed during treatment. Median follow-up time after treatment was 15 months. At 5 months, severe hypercalcemia was observed in two patients due to rebound increase in osteoclastic activity. Subsequent to denosumab treatment, three patients underwent surgery for clinical or radiological recurrence. CONCLUSIONS: Our results showed that denosumab provided a meaningful clinical and radiological improvement in ABC. It may be a treatment option, especially in spinal and pelvic tumors with potentially high surgical morbidity. However, late rebound hypercalcemia may restrict its use. Studies with more cases are required for routine use of denosumab in ABC.

Lipoblastoma in children: Review of 12 cases.

BACKGROUND: Lipoblastoma is a rare benign mesenchymal tumor of infancy and early childhood. Symptoms vary depending on localization, and signs of compression of adjacent organs may be seen. METHODS: A total of 12 children with pathologically proven lipoblastoma from 2000 to 2014 were reviewed retrospectively for their clinical features, treatment and follow up. RESULTS: There were seven boys and five girls between 7.5 months and 7.5 years of age. The most common symptom was painless rapid-growing mass. The tumors were located in the neck, the abdomen, the groin, pelvis, axilla, glutea, labium majus, thigh and trunk. The largest tumor was in a retroperitoneal location and was 13 × 10 cm in size. Complete resection was performed in 10 patients. All of these patients were followed without any evidence of recurrence. Subtotal excision was performed in two patients. At a median follow up of 38 months (range, 1.8 months-10 years), all patients were disease free. CONCLUSIONS: Lipoblastoma should be considered in the differential diagnosis of rapidly growing mass in patients <3 years of age. Total excision is the treatment of choice with preservation of vital organs. The prognosis is excellent despite large tumor size and local invasion. Recurrence rate is high in incompletely resected tumors. Regular follow up is important for early detection of recurrence.

Renal Late Effects After the Treatment of Unilateral Nonsyndromic Wilms Tumor.

Wilms tumor is the most common renal malignancy of childhood. Because of the improvement in prognosis and the increase in survival rates, long-term consequences of the treatment for Wilms tumor are of greater concern. We investigated late renal effects of the treatment on 50 survivors of nonsyndromic unilateral Wilms tumor. After the second year since the cessation of treatment, the glomerular filtration rate (GFR), urinary protein excretion, urinary ß2 microglobulin levels, and blood pressure as well as the general health status were assessed. Results were analyzed for correlation with clinical variables, chemotherapy, and radiotherapy as possible risk factors. At a median follow-up time of 8.8 years (mean=10.9; range, 2.3 to 35.4 y), none of the patients developed end-stage renal disease. Compensatory hypertrophy was observed in 68% of the cases. The median maximum bipolar length was significantly higher in patients diagnosed after the age of 36 months. Eleven (22%) and 2 (4%) of the 50 patients were hypertensive at the time of the diagnosis and the study, respectively. Similarly, median GFR values were significantly lower at the time of diagnosis, although at the time of the study, all patients had normal GFR values. With longer follow-up intervals, especially after 10 years, a significant decreasing trend in the GFR was observed (P=0.002).

High-dose chemotherapy and autologous haematopoietic stem cell rescue for children with high-risk neuroblastoma.

BACKGROUND: Despite the development of new treatment options, the prognosis of high-risk neuroblastoma patients is still poor; more than half of patients experience disease recurrence. High-dose chemotherapy and haematopoietic stem cell rescue (i.e. myeloablative therapy) might improve survival. This review is the second update of a previously published Cochrane review. OBJECTIVES: Primary objectiveTo compare the efficacy, that is event-free and overall survival, of high-dose chemotherapy and autologous bone marrow or stem cell rescue with conventional therapy in children with high-risk neuroblastoma. Secondary objectivesTo determine adverse effects (e.g. veno-occlusive disease of the liver) and late effects (e.g. endocrine disorders or secondary malignancies) related to the procedure and possible effects of these procedures on quality of life. SEARCH METHODS: We searched the electronic databases The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2014, issue 11), MEDLINE/PubMed (1966 to December 2014) and EMBASE/Ovid (1980 to December 2014). In addition, we searched reference lists of relevant articles and the conference proceedings of the International Society for Paediatric Oncology (SIOP) (from 2002 to 2014), American Society for Pediatric Hematology and Oncology (ASPHO) (from 2002 to 2014), Advances in Neuroblastoma Research (ANR) (from 2002 to 2014) and American Society for Clinical Oncology (ASCO) (from 2008 to 2014). We searched for ongoing trials by scanning the ISRCTN register (www.isrct.com) and the National Institute of Health Register (www.clinicaltrials.gov). Both registers were screened in April 2015. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing the efficacy of myeloablative therapy with conventional therapy in high-risk neuroblastoma patients. DATA COLLECTION AND ANALYSIS: Two authors independently performed study selection, data extraction and risk of bias assessment. If appropriate, we pooled studies. The risk ratio (RR) and 95% confidence interval (CI) was calculated for dichotomous outcomes. For the assessment of survival data, we calculated the hazard ratio (HR) and 95% CI. We used Parmar's method if hazard ratios were not reported in the study. We used a random-effects model. MAIN RESULTS: We identified three RCTs including 739 children. They all used an age of one year as the cut-off point for pre-treatment risk stratification. The first updated search identified a manuscript reporting additional follow-up data for one of these RCTs, while the second update identified an erratum of this study. There was a significant statistical difference in event-free survival in favour of myeloablative therapy over conventional chemotherapy or no further treatment (three studies, 739 patients; HR 0.78, 95% CI 0.67 to 0.90). There was a significant statistical difference in overall survival in favour of myeloablative therapy over conventional chemotherapy or no further treatment (two studies, 360 patients; HR 0.74, 95% CI 0.57 to 0.98). However, when additional follow-up data were included in the analyses the difference in event-free survival remained statistically significant (three studies, 739 patients; HR 0.79, 95% CI 0.70 to 0.90), but the difference in overall survival was no longer statistically significant (two studies, 360 patients; HR 0.86, 95% CI 0.73 to 1.01). The meta-analysis of secondary malignant disease and treatment-related death did not show any significant statistical differences between the treatment groups. Data from one study (379 patients) showed a significantly higher incidence of renal effects, interstitial pneumonitis and veno-occlusive disease in the myeloablative group compared to conventional chemotherapy, whereas for serious infections and sepsis no significant difference between the treatment groups was identified. No information on quality of life was reported. In the individual studies we evaluated different subgroups, but the results were not univocal in all studies. All studies had some methodological limitations. AUTHORS' CONCLUSIONS: Based on the currently available evidence, myeloablative therapy seems to work in terms of event-free survival. For overall survival there is currently no evidence of effect when additional follow-up data are included. No definitive conclusions can be made regarding adverse effects and quality of life, although possible higher levels of adverse effects should be kept in mind. A definitive conclusion regarding the effect of myeloablative therapy in different subgroups is not possible. This systematic review only allows a conclusion on the concept of myeloablative therapy; no conclusions can be made regarding the best treatment strategy. Future trials on the use of myeloablative therapy for high-risk neuroblastoma should focus on identifying the most optimal induction and/or myeloablative regimen. The best study design to answer these questions is a RCT. These RCTs should be performed in homogeneous study populations (e.g. stage of disease and patient age) and have a long-term follow-up. Different risk groups, using the most recent definitions, should be taken into account.It should be kept in mind that recently the age cut-off for high risk disease was changed from one year to 18 months. As a result it is possible that patients with what is now classified as intermediate-risk disease have been included in the high-risk groups. Consequently the relevance of the results of these studies to the current practice can be questioned. Survival rates may be overestimated due to the inclusion of patients with intermediate-risk disease.

Secretory breast carcinoma in a 6-year-old girl: mastectomy with sentinel lymph node dissection.

Secretory breast carcinoma (SBC) is a rare type of breast neoplasia that was originally described in children. SBC is an indolent breast tumor with good clinical outcome and rare systemic involvement. Since, majority of studies concerning pediatric SBC have been case reports, it has been difficult to clearly elucidate the characteristics and optimal treatment strategies for SBC in children. Although treatment recommendations vary, surgical excision is the primary mode of treatment. Also, necessity of axillary and/or sentinel lymph node dissection is another matter of discussion in children. We report a 6-year-old girl who was diagnosed as SBC was reported to discuss the use of mastectomy with sentinel lymph node dissection in the treatment of this rare tumor in children.

Pure endobronchial inflammatory myofibroblastic tumor in children.

Isolated endobronchial inflammatory myofibroblastic tumor is an unusual diagnosis among endobronchial masses in childhood. The presenting signs and symptoms may mimic asthma. Rigid bronchoscopy is effective for the diagnosis and treatment. Follow-up is mandatory to check for recurrent disease. Here in, the authors report on a 9-year-old girl with endobronchial inflammatory myofibroblastic tumor to emphasize the possibility of endobronchial lesion in children with longstanding obstructive symptoms.

Salivary gland tumors in children: a retrospective clinical review.

Seven patients with salivary gland tumors who underwent between 1972 and 2012 were retrospectively evaluated. The age of the patients ranged from 6.3 to 13 years old; five were females and two were males. Five patients had stage IVa, one patient had stage I, and one patient had stage II disease. The surgical margin was found to be positive in five cases. There were three adenoid cystic carcinoma, two adenocarcinoma, one anaplastic carcinoma, and one mucoepidermoid carcinoma. There were five parotid, one lacrimal gland, and one palatal involvement. Three patients who had low stage tumors were treated with surgery alone. Four of the cases received adjuvant radiation and chemotherapy. One patient with parotid tumor died with progressive disease. One case with lacrimal gland neoplasm was alive 48 months after discontinuation of treatment. The other palate case was lost to follow-up 1 month after the beginning of the treatment. Surgery is the primary treatment, with radiotherapy and chemotherapy used as adjuvant treatments. The treatment options need to be selected and planned for each individual patient.

Clinical features and treatment results of children with diffuse large B-cell lymphoma.

The demographic, clinical characteristics, and treatment groups of 33 children with diffuse large B-cell lymphoma (DLBCL) were recorded and analyzed among 1486 non-Hodgkin lymphoma (NHL) cases since 1972. The median age was 9.7 years (range 1.4-16.9) and male/female ratio was 24/9 = 2.6. Kaplan-Meier methods and logrank tests were used in treatment analysis. The frequency of DLBCL among 1486 NHL cases was 2.2%, however, the percentage was 9.3% in cases diagnosed after 2000. The event-free survival (EFS) and overall survival (OS) rates for 33 children were 61% and 65.1% at 5 years, respectively. The EFS and OS rates of low stage (stages I and II) disease decreased to lower level in advanced stage (stages III and IV) disease. Associated conditions and ages older than 14 years were found as poor prognostic factors in multivariate analysis. The survival rates in children with DLBCL need further improvement. This is mainly related with late referral of those children with advanced disease. The proper diagnosis and early referral is essential in these children for a better survival rate. The children with associated conditions and older children must be handled with care since these are found as poor prognostic factors.

Ganglioneuromas in Childhood: Hacettepe Experience With 70 Cases.

BACKGROUND: Ganglioneuromas (GNs) are rare benign peripheral neuroblastic tumors (PNTs). We shared our institutional experience with childhood GNs. METHODS: Records of the children with PNTs between January 1995 and December 2021 were reviewed, and cases with histopathological diagnoses of GN were identified. Clinical, laboratory, radiological, and histopathological findings, image-defined risk factors (IDRFs), procedures, and overall outcomes were recorded. RESULTS: Of 668 cases with PNTs, 70 (10.4%) had GNs. The median age was 7.4 years (range, 2.6-15.7 years) (girls/boys, 41/29). Common presenting complaints were abdominal pain and cough; 33/70 cases (47.1%) were diagnosed incidentally. Primary tumors were in the abdomen in 41/70, the thorax in 25/70, the neck in 3 cases, and the pelvis in one. The median tumor size was 6.5 cm (range, 1.4-17). Fifty cases (71.4%) were staged as INRG-L1; 20 cases with IDRFs (15 single, five >1) were staged as INRG-L2. Complete and partial tumor resections were performed in 58/70 and 6/70 cases, while 6 had no resection. The overall complication rate was 17.1% (11/64). At a median follow-up of 9 years, five were lost to follow-up; 65 were alive. One patient with gross residue underwent total resection due to progression 13 years after the surgery, and one in the unresected group was lost to follow-up. Ten other cases without a complete resection experienced no tumor progression. CONCLUSIONS: Ganglioneuromas are benign PNTs, and most are free of IDRFs. Even without complete resection, long-term outcomes are excellent. Guidelines should be devised considering the high surgical complication rates and benign course of GNs. LEVEL OF EVIDENCE: Case series, IV.

International consensus on mitotane treatment in pediatric patients with adrenal cortical tumors: indications, therapy, and management of adverse effects.

OBJECTIVE: Mitotane is an important cornerstone in the treatment of pediatric adrenal cortical tumors (pACC), but experience with the drug in the pediatric age group is still limited and current practice is not guided by robust evidence. Therefore, we have compiled international consensus statements from pACC experts on mitotane indications, therapy, and management of adverse effects. METHODS: A Delphi method with 3 rounds of questionnaires within the pACC expert consortium of the international network groups European Network for the Study of Adrenal Tumors pediatric working group (ENSAT-PACT) and International Consortium of pediatric adrenocortical tumors (ICPACT) was used to create 21 final consensus statements. RESULTS: We divided the statements into 4 groups: environment, indications, therapy, and adverse effects. We reached a clear consensus for mitotane treatment for advanced pACC with stages III and IV and with incomplete resection/tumor spillage. For stage II patients, mitotane is not generally indicated. The timing of initiating mitotane therapy depends on the clinical condition of the patient and the setting of the planned therapy. We recommend a starting dose of 50 mg/kg/d (1500 mg/m²/d) which can be increased up to 4000 mg/m2/d. Blood levels should range between 14 and 20 mg/L. Duration of mitotane treatment depends on the clinical risk profile and tolerability. Mitotane treatment causes adrenal insufficiency in virtually all patients requiring glucocorticoid replacement shortly after beginning. As the spectrum of adverse effects of mitotane is wide-ranging and can be life-threatening, frequent clinical and neurological examinations (every 2-4 weeks), along with evaluation and assessment of laboratory values, are required. CONCLUSIONS: The Delphi method enabled us to propose an expert consensus statement, which may guide clinicians, further adapted by local norms and the individual patient setting. In order to generate evidence, well-constructed studies should be the focus of future efforts.

Educational achievement, employment, smoking, marital, and insurance statuses in long-term survivors of childhood malignant solid tumors.

BACKGROUND/OBJECTIVE: Survivors of childhood cancer experience many social adaptation problems. We aimed to identify social, educational, and occupational issues of this growing population. PATIENTS AND METHODS: Survivors treated for childhood malignant solid tumors who were older than 18 years and in remission for at least 3 years were surveyed. The educational achievement, employment, type of habitation, marital status, parenthood, social insurance, and smoking status of the patients were inquired and recorded. RESULTS: Two hundred one patients (126 male patients/75 female patients) were included in the study between 2007 and 2009. The median ages at the time of diagnosis and at the time of study were 10 years (range, 0 to 19 y) and 23 years (range, 18 to 39 y), respectively. The median follow-up duration was 13.5 years (range, 3 to 31 y). Nearly half of the participants were lymphoma survivors. One hundred eleven (55.5%) survivors were high school graduates and 47 (23%) were university graduates. Unemployment rate was 36.8%. Public social insurance rate was 90.5%. Fifty-three (26.4%) survivors had independent habitation. Thirty percent of survivors were married and 7.5% had at least 1 child. Marriage rates were significantly higher in survivors who were older than 23 years, had a follow-up duration of >13 years, had a job, and lived independently (for each parameter P=0.001). University degree was significantly lower in survivors who were treated for central nervous system tumors. CONCLUSIONS: Our results have drawn a more marked picture with lower educational achievement and marital rates when compared with the results of large survivorship studies conducted in developed countries. However, they can be interpreted as intriguing when limited resources are taken into account.

High-dose chemotherapy and autologous haematopoietic stem cell rescue for children with high-risk neuroblastoma.

BACKGROUND: Despite the development of new treatment options, the prognosis of high-risk neuroblastoma patients is still poor; more than half of patients experience disease recurrence. High-dose chemotherapy and haematopoietic stem cell rescue (i.e. myeloablative therapy) might improve survival. This review is an update of a previously published Cochrane review. OBJECTIVES: The primary objective was to compare the efficacy of myeloablative therapy with conventional therapy in children with high-risk neuroblastoma. Secondary objectives were to determine possible effects of these interventions on adverse events, late effects and quality of life. SEARCH METHODS: We searched the electronic databases CENTRAL (The Cochrane Library 2012, issue 6), MEDLINE/PubMed (1966 to June 2012) and EMBASE/Ovid (1980 to June 2012). In addition, we searched reference lists of relevant articles and the conference proceedings of the International Society for Paediatric Oncology (SIOP) (from 2002 to 2011), American Society for Pediatric Hematology and Oncology (ASPHO) (from 2002 to 2012), Advances in Neuroblastoma Research (ANR) (from 2002 to 2012) and American Society for Clinical Oncology (ASCO) (from 2008 to 2012). We searched for ongoing trials by scanning the ISRCTN register and the National Institute of Health Register (http://www.controlled-trials.com; both screened July 2012). SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing the efficacy of myeloablative therapy with conventional therapy in high-risk neuroblastoma patients. DATA COLLECTION AND ANALYSIS: Two authors independently performed study selection, data extraction and risk of bias assessment. If appropriate, we pooled studies. The risk ratio (RR) and 95% confidence interval (CI) was calculated for dichotomous outcomes. For the assessment of survival data, we calculated the hazard ratio (HR) and 95% CI. We used Parmar's method if hazard ratios were not reported in the study. We used a random-effects model. MAIN RESULTS: We identified three RCTs including 739 children. They all used an age of one year as the cut-off point for pre-treatment risk stratification. The updated search identified a manuscript reporting additional follow-up data for one of these RCTs. There was a statistically significant difference in event-free survival in favour of myeloablative therapy over conventional chemotherapy or no further treatment (3 studies, 739 patients; HR 0.78, 95% CI 0.67 to 0.90). There was a statistically significant difference in overall survival in favour of myeloablative therapy over conventional chemotherapy or no further treatment (2 studies, 360 patients; HR 0.74, 95% CI 0.57 to 0.98). However, when additional follow-up data were included in the analyses the difference in event-free survival remained statistically significant (3 studies. 739 patients; HR 0.79, 95% CI 0.70 to 0.90), but the difference in overall survival was no longer statistically significant (2 studies, 360 patients; HR 0.86, 95% CI 0.73 to 1.01). The meta-analysis of secondary malignant disease and treatment-related death did not show any statistically significant differences between the treatment groups. Data from one study (379 patients) showed a significantly higher incidence of renal effects, interstitial pneumonitis and veno-occlusive disease in the myeloablative group compared to conventional chemotherapy, whereas for serious infections and sepsis no significant difference between the treatment groups was identified. No information on quality of life was reported. In the individual studies we evaluated different subgroups, but the results were not univocal in all studies. All studies had some methodological limitations. AUTHORS' CONCLUSIONS: Based on the currently available evidence, myeloablative therapy seems to work in terms of event-free survival. For overall survival there is currently no evidence of effect when additional follow-up data are included. No definitive conclusions can be made regarding adverse effects and quality of life, although possible higher levels of adverse effects should be kept in mind. A definitive conclusion regarding the effect of myeloablative therapy in different subgroups is not possible. This systematic review only allows a conclusion on the concept of myeloablative therapy; no conclusions can be made regarding the best treatment strategy. Future trials on the use of myeloablative therapy for high-risk neuroblastoma should focus on identifying the most optimal induction and/or myeloablative regimen. The best study design to answer these questions is a RCT. These RCTs should be performed in homogeneous study populations (e.g. stage of disease and patient age) and have a long-term follow-up. Different risk groups, using the most recent definitions, should be taken into account.It should be kept in mind that recently the age cut-off for high risk disease was changed from one year to 18 months. As a result it is possible that patients with what is now classified as intermediate-risk disease have been included in the high-risk groups. Consequently the relevance of the results of these studies to the current practice can be questioned. Survival rates may be overestimated due to the inclusion of patients with intermediate-risk disease.

Evaluation of patients with intracranial tumors and central diabetes insipidus.

The aim of the study is to evaluate the etiologic and clinical characteristics, treatment regimens, and outcome of the patients with intracranial tumors presenting with central diabetes insipidus (DI). Sixty-nine patients with intracranial tumors presenting with central DI between 1972 and 2012 were retrospectively evaluated. Fifty-three out of 69 patients were included in the analysis. Male/female ratio was 1.52, median age was 7.6 years. Of 53 patients, 37 patients (69.8%) were diagnosed with Langerhans cell histiocytosis, 14 patients (26.4%) with germinoma, 1 (1.9%) with astrocytoma, and 1 (1.9%) with optic glioma. 10-year overall survival (OS) rate and disease-free survival rate for all patients were 91.7% and 52%. 10-year OS rate according to diagnostic criteria was 91% for Langerhans cell histiocytosis (LCH) cases, 79% for intracranial germinoma, which was statistically significant (P = .0001). Central DI may be very important clinical presentation of serious underlying disease in children. Intracranial tumors are the most frequent cause of DI. Most frequent diagnosis were LCH and germ cell tumors in our series.

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.