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Study Question: Which treatment-related factors are (dose-dependently) associated with abnormal hormonal and ultrasound markers of ovarian reserve in female childhood cancer survivors (CCSs)?Summary Answer: Cyclophosphamide, procarbazine, a composite group of 'other alkylating agents', dactinomycin, doxorubicin, mitoxantrone, spinal radiotherapy (RT), abdominal/pelvic RT and total body irradiation were multivariably associated with abnormal ovarian reserve markers, with dose-effect relationships being established for procarbazine and abdominal/pelvic RT.What Is Known Already: Female childhood cancer survivors are at an increased risk of reduced ovarian function and reserve, but knowledge regarding the long-term effects of individual chemotherapeutic (CT) agents and radiotherapy fields and their respective doses is limited.Study Design, Size, Duration: The DCOG LATER-VEVO is a nationwide retrospective cohort study in which measurements were performed between 2008 and 2014. In total, 1749 female 5-year CCSs, diagnosed before age 18 years between 1963 and 2002 and 1201 controls were invited for the study.Participants/materials, Setting, Methods: Ovarian reserve was assessed by anti-Müllerian hormone (AMH), follicle stimulating hormone (FSH), inhibin B levels, and antral follicle counts (AFC). The study was a multicentre study including all seven Dutch Centers for Paediatric Oncology/Haematology.Main Results and the Role Of Chance: In total, 564 CCs and 390 controls participated in the clinical part of the study. Overall, 7.0-17.7% of CCSs and 2.4-13.6% of controls had abnormal ovarian reserve markers. Above age 35, significantly more CCSs than controls had abnormal ovarian reserve markers (AMH: 26% vs. 4%; AFC: 20% vs. 3%; inhibin B: 42% vs. 16%). For AMH and FSH, significant differences were also found below age 35. Cyclophosphamide, procarbazine, a group of 'other alkylating agents', dactinomycin, doxorubicin, mitoxantrone, spinal RT, abdominal/pelvic RT and total body irradiation were multivariably associated with at least one abnormal ovarian reserve marker. Dose-effect relationships were established for procarbazine and abdominal/pelvic RT.Limitations, Reasons For Caution: Despite the large scale of the study, dose-effect relationships could not be investigated for all types of treatment due to a limited numbers of participants for specific analyses.Wider Implications Of the Findings: This study demonstrated that the majority of CCSs do not show signs of a reduced ovarian reserve. However, specific subgroups of CCSs appear to be associated with a high risk. Our results are important for counselling CCSs and future patients regarding parenthood and fertility preservation.Study Funding/competing Interests: This study was funded by the Dutch Cancer Society (Grant no. VU 2006-3622) and by the Children Cancer Free Foundation (Project no. 20). Philips Health Systems Benelux supported this study by providing three ultrasound systems and concomitant analytic software. There are no competing interests.Trial Registration Number: NTR2922 http://www.trialregister.nl/trialreg/admin/rctview.asp?TC = 2922. [ABSTRACT FROM AUTHOR]

Study Question: Do female childhood cancer survivors (CCSs) express a decreased desire to have children and do they use reproductive health care more often compared to women without a history of cancer?Summary Answer: Overall, no difference was found in the desire to have children between CCSs and controls, whereas CCSs consult a fertility specialist more often, at a younger age, and sooner after their first attempt at conceiving.What Is Known Already: Female CCSs may face a shorter than anticipated reproductive window as a result of their cancer treatment. Little is known about their desire to have children and use of reproductive health care, especially in relation to their former cancer treatment.Study Design, Size, Duration: This study is part of the DCOG LATER-VEVO study, a nationwide retrospective cohort study on female fertility in Dutch CCSs. In total, 1749 CCSs and 1673 controls were invited for the study. Data collection took place between January 2008 and May 2014.Participants/materials, Setting, Methods: Data on the desire to have children and use of reproductive health care were collected by questionnaire. The control group consisted of sisters from CCSs and females from the general population. In total, 1106 (63%) CCSs and 818 (49%) controls completed the questionnaire.Main Results and the Role Of Chance: Overall, no difference was found in the desire to have children between CCSs and controls (86% and 89%, respectively). However, survivors of a CNS tumour were less likely to desire children and CCSs without biological children at time of study were more likely to report that their desire to have children was unfulfilled because of medical reasons (9%), compared to controls (1%). In total, 12% of CCSs ever consulted a fertility specialist compared to 10% of controls (OR = 1.7, 95% CI: 1.3-2.4). Mean (SD) age at time of their first visit was 27.7 (4.4) years for CCSs and 29.9 (3.9) years for controls (P < 0.01). In total, 43% of CCSs consulted a fertility specialist within 12 months after they had started trying to achieve a pregnancy, compared to 27% of controls. Risk factors for consulting a fertility specialist included a previous diagnosis of renal tumour, leukaemia, lymphoma or a CNS tumour, and treatment with alkylating chemotherapy, gonadotoxic radiotherapy or both. In total, 70% of CCSs reported a female factor as cause of subfertility compared to 34% of controls (OR = 4.5, 95% CI: 2.3-8.7) and in this specific group, CCSs seemed more likely to use fertility treatment (OR = 2.9, 95% CI: 1.0-8.2).Limitations, Reasons For Caution: Because of the low number of CCSs who used fertility treatment, we were not able to look at specific diagnoses and treatment types associated with using fertility treatment. Nevertheless, we were able to identify diagnostic- and treatment-related risk factors for consulting a fertility specialist. Details regarding consultations with a fertility specialist and fertility treatment were based on self-report and may therefore be subject to recall bias.Wider Implications Of the Findings: Decisions about parenthood affect all CCSs. It's important to evaluate reproductive intentions and function timely after cancer treatment, so CCSs can be adequately counselled regarding family planning and fertility treatment.Study Funding/competing Interest(s): This work was supported by the Dutch Cancer Society (Grant no. VU 2006-3622) and the Children Cancer Free Foundation (Project no. 20).Trial Registration Number: NTR2922. [ABSTRACT FROM AUTHOR]

Background: Treatment for childhood cancer may increase the risk of long-term pulmonary complications and dysfunction. Pulmonary surveillance is recommended after established pulmonary toxic exposures, including bleomycin, busulfan, carmustine (BCNU), lomustine (CCNU), radiotherapy to a field exposing the lungs, and pulmonary surgery. However, the role of cyclophosphamide as a pulmonary toxic agent is debated., Aim: To establish whether cyclophosphamide is associated with late pulmonary dysfunction among survivors of childhood cancer., Methods: In this multicenter Dutch Childhood Cancer Survivor Study (DCCSS)-LATER 2 PULM sub-study, we included 828 survivors with a median follow-up of 26.6 years, treated with cyclophosphamide and/or established pulmonary toxic treatment, or neither. Pulmonary function tests were used to measure the primary outcomes of diffusion impairment (diffusing capacity for carbon monoxide (DLCO) z-score), restriction (total lung capacity (TLC) z-score), and obstruction (forced expiratory volume in the first second/forced vital capacity (FEV1/FVC) z-score). Secondary outcomes comprised chronic cough, recurrent respiratory tract infections, shortness of breath, and supplemental oxygen need., Results: Diffusion and restrictive abnormalities were highly prevalent among those treated with established pulmonary toxic treatment, with cyclophosphamide (41.0 % and 50.4 %, respectively) and without (34.3 % and 41.9 %, respectively), and occurred less frequently in survivors treated with cyclophosphamide only (12.9 % and 7.3 %, respectively) or in survivor controls (9.9 % and 12.4 %, respectively). In multivariable analyses, cyclophosphamide did not have a clinically relevant effect on the primary or secondary outcomes., Conclusions: This study suggests that cyclophosphamide is not associated with clinically relevant pulmonary dysfunction in long-term childhood cancer survivors., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 Elsevier Ltd. All rights reserved.)

Background & Aims: A dysfunctional hypothalamus may result in decreased feelings of satiety (hyperphagia), decreased energy expenditure, and increased fat storage as a consequence of hyperinsulinemia. Hypothalamic dysfunction may thus lead to morbid obesity and can be encountered in childhood as a consequence of congenital, genetic, or acquired disorders. There is currently no effective treatment for hypothalamic obesity (HO). However, comparable to alimentary obesity, dietary and lifestyle interventions may be considered the cornerstones of obesity treatment. We questioned the effect of dietary or lifestyle interventions for HO and systematically searched the literature for evidence on feasibility, safety, or efficacy of dietary or lifestyle interventions for childhood hypothalamic overweight or obesity., Methods: A systematic search was conducted in MEDLINE (including Cochrane Library), EMBASE, and CINAHL (May 2023). Studies assessing feasibility, safety, or efficacy of any dietary or lifestyle intervention in children with hypothalamic overweight or obesity, were included. Animal studies, studies on non-diet interventions, and studies with no full text available were excluded. Because the number of studies to be included was low, the search was repeated for adults with hypothalamic overweight or obesity. Risk of bias was assessed with an adapted Cochrane Risk of Bias Tool. Level of evidence was assessed using the GRADE system. Descriptive data were described, as pooled-data analysis was not possible due to heterogeneity of included studies., Results: In total, twelve studies were included, with a total number of 118 patients (age 1-19 years) of whom one with craniopharyngioma, one with ROHHAD-NET syndrome, 50 with monogenic obesity, and 66 with Prader-Willi syndrome (PWS). Four studies reported a dietary intervention as feasible. However, parents did experience difficulties with children still stealing food, and especially lowering carbohydrates was considered to be challenging. Seven studies reported on efficacy of a dietary intervention: a well-balanced restrictive caloric diet (30% fat, 45% carbohydrates, and 25% protein) and various hypocaloric diets (8-10 kcal/cm/day) were considered effective in terms of weight stabilization or decrease. No negative effect on linear growth was reported. Four studies reported on specific lifestyle interventions, of which three also included a dietary intervention. Combined dietary and lifestyle intervention resulted in decreased BMI, although BMI returned to baseline values on long-term. One additional study was identified in adults after brain trauma and showed a significant reduction in BMI in one out of eight patients after a combined dietary and lifestyle intervention., Conclusions: Hypocaloric diet or restrictive macronutrient diet with lower percentage of carbohydrates seems feasible and effective for childhood HO, although most of the studies had a high risk of bias, small cohorts without control groups, and were conducted in children with PWS only, compromising the generalizability. Lifestyle interventions only resulted in BMI decrease in short-term, indicating that additional guidance is needed to sustain its effect in the long-term. Literature on feasibility and efficacy of a dietary or lifestyle intervention for hypothalamic overweight or obesity is scarce, especially in children with acquired HO (following treatment for a suprasellar tumor). There is need for prospective (controlled) studies to determine which dietary and lifestyle intervention are most helpful for this specific patient group., Competing Interests: Conflict of interest None of the authors report a conflict of interest., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objectives: Invasive Aspergillus infections during the early phase of childhood acute lymphoblastic leukemia (ALL) treatment come with morbidity and mortality. The interaction with vincristine hampers first-line azole prophylaxis. We describe the efficacy of an alternative twice-a-week micafungin regimen for Aspergillus prophylaxis., Methods: Newly diagnosed paediatric patients with ALL treated according to the ALL-11 protocol received micafungin twice-a-week (9 mg/kg/dose [max. 300 mg]) during the induction course (first 35 days of treatment) as part of routine care. A historical control cohort without Aspergillus prophylaxis was used. During the first consolidation course (day 36-79), standard itraconazole prophylaxis was used in both groups. The percentage of proven/probable Aspergillus infections during the induction/first consolidation course was compared between the cohorts. The cumulative incidence of proven/probable Aspergillus infections was estimated using a competing risk model. For safety evaluation, liver laboratory chemistry values were analysed., Results: A total of 169 and 643 paediatric patients with ALL were treated in the micafungin cohort (median age: 4 years [range 1-17]) and historical cohort (median age: 5 years [range 1-17]). The percentage of proven/probable Aspergillus infections was 1·2% (2/169) in the micafungin cohort versus 5·8% (37/643) in the historical cohort (p=0.013; Fisher's exact test). The differences in estimated cumulative incidence were assessed (p=0·014; Gray's test). Although significantly higher ALT/AST values were reported in the micafungin cohort, no clinically relevant side effects were observed., Conclusions: Twice-a-week micafungin prophylaxis during the induction course significantly reduced the occurrence of proven/probable Aspergillus infections in the early phase of childhood ALL treatment., (Copyright © 2023. Published by Elsevier Ltd.)

Background: The purpose of this study was to determine factors associated with chronic fatigue (CF) in childhood cancer survivors (CCS)., Patients and Methods: Participants were included from the Dutch Childhood Cancer Survivor Study (DCCSS) LATER cohort, a nationwide cohort of CCS (≥5 years after diagnosis) and siblings as controls. Fatigue severity was assessed with the 'fatigue severity subscale' of the Checklist Individual Strength ('CIS-fatigue'). CF was defined as scoring ≥35 on the 'CIS-fatigue' and having fatigue symptoms for ≥6 months. Twenty-four parameters were assessed, categorized into assumed fatigue triggering, maintaining and moderating factors. Multivariable logistic regression analyses were carried out to investigate the association of these factors with CF., Results: A total of 1927 CCS participated in the study (40.7% of invited cohort), of whom 23.6% reported CF (compared with 15.6% in sibling controls, P < 0.001). The following factors were associated with CF: obesity [versus healthy weight, odds ratio (OR) 1.93; 95% confidence interval (CI) 1.30-2.87], moderate physical inactivity (versus physical active, OR 2.36; 95% CI 1.67-3.34), poor sleep (yes versus no, OR 2.03; 95% CI 1.54-2.68), (sub)clinical anxiety (yes versus no, OR 1.55; 95% CI 1.10-2.19), (sub)clinical depression (yes versus no, OR 2.07; 95% CI 1.20-3.59), pain (continuous, OR 1.49; 95% CI 1.33-1.66), self-esteem (continuous, OR 0.95; 95% CI 0.92-0.98), helplessness (continuous, OR 1.13; 95% CI 1.08-1.19), social functioning (continuous, OR 0.98; 95% CI 0.97-0.99) and female sex (versus male sex, OR 1.79; 95% CI 1.36-2.37)., Conclusion: CF is a prevalent symptom in CCS that is associated with several assumed maintaining factors, with lifestyle and psychosocial factors being the most prominent. These are modifiable factors and may therefore be beneficial to prevent or reduce CF in CCS., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

In children with cancer, the heterogeneity in ototoxicity occurrence after similar treatment suggests a role for genetic susceptibility. Using a genome-wide association study (GWAS) approach, we identified a genetic variant in TCERG1L (rs893507) to be associated with hearing loss in 390 non-cranial irradiated, cisplatin-treated children with cancer. These results were replicated in two independent, similarly treated cohorts (n = 192 and 188, respectively) (combined cohort: P = 5.3 × 10 -10 , OR 3.11, 95% CI 2.2-4.5). Modulating TCERG1L expression in cultured human cells revealed significantly altered cellular responses to cisplatin-induced cytokine secretion and toxicity. These results contribute to insights into the genetic and pathophysiological basis of cisplatin-induced ototoxicity., (© 2021. The Author(s).)

Aim: To investigate the health-related quality of life (HRQOL) of Dutch adult childhood cancer survivors (CCS) and to identify risk factors of impaired HRQOL., Methods: Adult CCS (age >18, diagnosed <18, ≥5 years since diagnosis) from the Dutch LATER registry completed the Medical Outcome Study Short Form 36 (SF-36) to measure HRQOL and provided sociodemographic characteristics. Age-adjusted mean SF-36 scale scores of CCS were compared to the Dutch general population for men and women separately using t-tests, with effect size d. Multivariate logistic regression models were built to identify sociodemographic and cancer-related risk factors for impaired physical and mental HRQOL., Results: Both male and female CCS (N = 2301, mean age = 35.4 years, 49.6% female) reported significantly (p ≤ .005) worse HRQOL than the general population on almost all scales of the SF-36 (-.11 ≤ d ≤ -.56). Largest differences were found on vitality and general health perceptions. Significant risk factors (p ≤ .05) for impaired physical HRQOL were female sex, older age at diagnosis, not having a partner, low educational attainment, disease recurrence and exposure to radiotherapy, specifically to lower extremity radiation. Odds ratios (ORs) ranged from 1.6 to 3.7. Significant risk factors for impaired mental HRQOL were age 26-35 years, male sex, not having a partner and low educational attainment. ORs ranged from 1.3 to 2.0., Conclusion: Adult CCS had worse HRQOL than the general population. CCS most at risk were those with low educational attainment and without a partner. Adult CCS could benefit from routine surveillance of their HRQOL. Special attention for CCS' vitality and health perceptions and beliefs is warranted., Competing Interests: Conflict of interest statement The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Study Question: Which treatment-related factors are (dose-dependently) associated with abnormal hormonal and ultrasound markers of ovarian reserve in female childhood cancer survivors (CCSs)?, Summary Answer: Cyclophosphamide, procarbazine, a composite group of 'other alkylating agents', dactinomycin, doxorubicin, mitoxantrone, spinal radiotherapy (RT), abdominal/pelvic RT and total body irradiation were multivariably associated with abnormal ovarian reserve markers, with dose-effect relationships being established for procarbazine and abdominal/pelvic RT., What Is Known Already: Female childhood cancer survivors are at an increased risk of reduced ovarian function and reserve, but knowledge regarding the long-term effects of individual chemotherapeutic (CT) agents and radiotherapy fields and their respective doses is limited., Study Design, Size, Duration: The DCOG LATER-VEVO is a nationwide retrospective cohort study in which measurements were performed between 2008 and 2014. In total, 1749 female 5-year CCSs, diagnosed before age 18 years between 1963 and 2002 and 1201 controls were invited for the study., Participants/materials, Setting, Methods: Ovarian reserve was assessed by anti-Müllerian hormone (AMH), follicle stimulating hormone (FSH), inhibin B levels, and antral follicle counts (AFC). The study was a multicentre study including all seven Dutch Centers for Paediatric Oncology/Haematology., Main Results and the Role of Chance: In total, 564 CCs and 390 controls participated in the clinical part of the study. Overall, 7.0-17.7% of CCSs and 2.4-13.6% of controls had abnormal ovarian reserve markers. Above age 35, significantly more CCSs than controls had abnormal ovarian reserve markers (AMH: 26% vs. 4%; AFC: 20% vs. 3%; inhibin B: 42% vs. 16%). For AMH and FSH, significant differences were also found below age 35. Cyclophosphamide, procarbazine, a group of 'other alkylating agents', dactinomycin, doxorubicin, mitoxantrone, spinal RT, abdominal/pelvic RT and total body irradiation were multivariably associated with at least one abnormal ovarian reserve marker. Dose-effect relationships were established for procarbazine and abdominal/pelvic RT., Limitations, Reasons for Caution: Despite the large scale of the study, dose-effect relationships could not be investigated for all types of treatment due to a limited numbers of participants for specific analyses., Wider Implications of the Findings: This study demonstrated that the majority of CCSs do not show signs of a reduced ovarian reserve. However, specific subgroups of CCSs appear to be associated with a high risk. Our results are important for counselling CCSs and future patients regarding parenthood and fertility preservation., Study Funding/competing Interests: This study was funded by the Dutch Cancer Society (Grant no. VU 2006-3622) and by the Children Cancer Free Foundation (Project no. 20). Philips Health Systems Benelux supported this study by providing three ultrasound systems and concomitant analytic software. There are no competing interests., Trial Registration Number: NTR2922 http://www.trialregister.nl/trialreg/admin/rctview.asp?TC = 2922., (© The Author(s) 2018. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Study Question: Do female childhood cancer survivors (CCSs) express a decreased desire to have children and do they use reproductive health care more often compared to women without a history of cancer?, Summary Answer: Overall, no difference was found in the desire to have children between CCSs and controls, whereas CCSs consult a fertility specialist more often, at a younger age, and sooner after their first attempt at conceiving., What Is Known Already: Female CCSs may face a shorter than anticipated reproductive window as a result of their cancer treatment. Little is known about their desire to have children and use of reproductive health care, especially in relation to their former cancer treatment., Study Design, Size, Duration: This study is part of the DCOG LATER-VEVO study, a nationwide retrospective cohort study on female fertility in Dutch CCSs. In total, 1749 CCSs and 1673 controls were invited for the study. Data collection took place between January 2008 and May 2014., Participants/materials, Setting, Methods: Data on the desire to have children and use of reproductive health care were collected by questionnaire. The control group consisted of sisters from CCSs and females from the general population. In total, 1106 (63%) CCSs and 818 (49%) controls completed the questionnaire., Main Results and the Role of Chance: Overall, no difference was found in the desire to have children between CCSs and controls (86% and 89%, respectively). However, survivors of a CNS tumour were less likely to desire children and CCSs without biological children at time of study were more likely to report that their desire to have children was unfulfilled because of medical reasons (9%), compared to controls (1%). In total, 12% of CCSs ever consulted a fertility specialist compared to 10% of controls (OR = 1.7, 95% CI: 1.3-2.4). Mean (SD) age at time of their first visit was 27.7 (4.4) years for CCSs and 29.9 (3.9) years for controls (P < 0.01). In total, 43% of CCSs consulted a fertility specialist within 12 months after they had started trying to achieve a pregnancy, compared to 27% of controls. Risk factors for consulting a fertility specialist included a previous diagnosis of renal tumour, leukaemia, lymphoma or a CNS tumour, and treatment with alkylating chemotherapy, gonadotoxic radiotherapy or both. In total, 70% of CCSs reported a female factor as cause of subfertility compared to 34% of controls (OR = 4.5, 95% CI: 2.3-8.7) and in this specific group, CCSs seemed more likely to use fertility treatment (OR = 2.9, 95% CI: 1.0-8.2)., Limitations, Reasons for Caution: Because of the low number of CCSs who used fertility treatment, we were not able to look at specific diagnoses and treatment types associated with using fertility treatment. Nevertheless, we were able to identify diagnostic- and treatment-related risk factors for consulting a fertility specialist. Details regarding consultations with a fertility specialist and fertility treatment were based on self-report and may therefore be subject to recall bias., Wider Implications of the Findings: Decisions about parenthood affect all CCSs. It's important to evaluate reproductive intentions and function timely after cancer treatment, so CCSs can be adequately counselled regarding family planning and fertility treatment., Study Funding/competing Interest(s): This work was supported by the Dutch Cancer Society (Grant no. VU 2006-3622) and the Children Cancer Free Foundation (Project no. 20)., Trial Registration Number: NTR2922.

Background: There is no international consensus on surveillance strategies for differentiated thyroid carcinoma (DTC) after radiotherapy for childhood cancer. Ultrasonography could allow for early detection of DTC, however, its value is yet unclear since the prognosis of DTC is excellent. We addressed the evidence for the question: 'is outcome of DTC influenced by tumor stage at diagnosis?'., Methods: A multidisciplinary working group answered the sub-questions: 'is recurrence or mortality influenced by DTC stage at diagnosis? Does detection of DTC at an early stage contribute to a decline in adverse events of treatment?' The literature was systematically reviewed, and conclusions were drawn based on the level of evidence (A: high, B: moderate to low, C: very low)., Results: In children, level C evidence was found that detection of DTC at an early stage is associated with lower recurrence and mortality rates. No evidence was found that it influences morbidity rates. In adults, clear evidence was found that less advanced staged DTC is a favorable prognostic factor for recurrence (level B) and mortality (level A). Additionally, it was found that more extensive surgery increases the risk to develop transient hypoparathyroidism (level A) and that higher doses of radioiodine increases the risk to develop second primary malignancies (level B)., Conclusion: Identification of DTC at an early stage is beneficial for children (very low level evidence) and adults (moderate to high level evidence), even considering that the overall outcome is excellent. These results are an important cornerstone for the development of guidelines for childhood cancer survivors at risk for DTC., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Aim: To assess systolic and diastolic function in adult childhood-cancer survivors (CCS) after treatment entailing potential cardiovascular toxicity., Methods: The study cohort consisted of 277 adult CCS (median age 28 [range 18-48]years), who had been treated with anthracyclines, platinum, and/or radiotherapy between 1976 and 1999, along with 130 healthy sibling controls. The assessments included echocardiography, baroreflex sensitivity measurement, and plasma N-terminal pro-brain natriuretic peptide (NT-proBNP). Echocardiography measurements were shortening fraction (SF) (abnormal<29%) for systolic function and tissue velocity imaging of early diastole (TVI Et) (abnormal<8.00)cm/sec for diastolic function; systolic function was also assessed by the wall motion score index (WMSI)., Results: At 18 (5-31)years post-treatment, the prevalence of both impaired SF and abnormal WMSI was increased in CCS compared to controls (p=0.003 and p<0.001, respectively). CCS also had an increased prevalence of diastolic dysfunction compared to the controls (12% versus 1%, p<0.001). Abnormal SF and/or abnormal diastolic function were found in 43% of CCS. NT-proBNP was higher in CCS and was associated to increased WMSI. Baroreflex sensitivity was lower in CCS and was associated with diastolic dysfunction. Systolic as well as diastolic dysfunction was associated with cumulative dose of anthracyclines and mediastinal irradiation., Conclusion: After treatment with potential cardiovascular toxic therapies, the risk of systolic and diastolic dysfunction in CCS is considerable. Since these abnormalities, in particular diastolic dysfunction, are age related, the observed effects might be considered a sign of precocious cardiac ageing., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

L-asparaginase is a key component of the antileukemic therapy in children with acute lymphoblastic leukemia (ALL). Pancreatitis has been noted to be a complication in 2-16% of patients undergoing treatment with L-asparaginase for a variety of pediatric neoplasms. Most cases of pancreatitis associated with L-asparaginase toxicity are self-limiting and respond favorably to nasogastric decompression and intravenous hyperalimentation. However, in rare instances, hemorrhagic pancreatitis or necrosis may occur. L-asparaginase-induced pancreatitis is an uncommon but potential lethal complication of the treatment of leukemia. We present a pediatric patient with leukemia and a severe, L-asparaginase-induced necrotizing pancreatitis, treated successfully with percutaneous drainage used to flush the infected necrotic parts., ((c) 2004 Wiley-Liss, Inc.)