Familial Currarino syndrome presenting with peripheral primitive neuroectodermal tumour arising with a sacral teratoma.

This report illustrates a rare genetic disorder, Currarino syndrome, in association with an unusual malignant transformation to a peripheral primitive neuroectodermal tumour within a sacral teratoma. The triad of features consists of a presacral mass, partial sacral agenesis and anorectal anomalies. The most common presentation is constipation. In this case there was a history of constipation, teratomas and spinal abnormalities in many of the family members over three generations. Detailed family history taken at time of initial presentation may have prevented delay in diagnosis and averted the need for intensive treatment, which may well cause late sequelae.

Transition guidelines: An important step in the future care for childhood cancer survivors. A comprehensive definition as groundwork.

Evidence-based clinical practice guidelines are essential to ensure that childhood cancer survivors at risk of chronic health conditions receive effective long-term follow-up care. However, adult survivors of childhood cancer are not always engaged in recommended health promotion and follow-up practices, as many centres do not have a formal transition programme that prepares survivors and their families for successful transfer from child-centred to adult-oriented healthcare. The need for a specific pan-European guideline for the transition of care for childhood cancer survivors has been recognised. The first step is to define the concept of transition of care for survivors of childhood cancer based on existing evidence.

Endocrine disorders among long-term survivors of childhood head and neck rhabdomyosarcoma.

PURPOSE: Head and neck rhabdomyosarcoma (HNRMS) survivors are at increased risk of developing pituitary dysfunction as an adverse event of radiotherapy. Our aim was to investigate the frequency and risk factors for pituitary dysfunction in these survivors. Secondly, we aimed to compare the prevalence of pituitary dysfunction between survivors treated with external beam radiation therapy (EBRT) and survivors treated with the ablative surgery, moulage technique after loading brachytherapy, and surgical reconstruction (AMORE) procedure. METHODS: Eighty HNRMS survivors treated in London (EBRT based) and Amsterdam (AMORE based: AMORE if feasible, otherwise EBRT) in the period 1990-2010 and alive ≥ 2 years post-treatment were evaluated. Survivors were evaluated in multidisciplinary late-effects clinics, with measurement of linear growth, determination of thyroid function, and growth hormone parameters. Additional data, such as baseline characteristics, anthropometrics, pubertal stage, and the results of additional laboratory investigations, were retrieved from patient charts. RESULTS: Pituitary dysfunction was diagnosed in 24 in 80 (30%) survivors, after a median follow-up time of 11 years. Median time to develop pituitary dysfunction after HNRMS diagnosis was 3.0 years. Risk factors were EBRT-based therapy (odds ratio [OR] 2.06; 95% confidence interval [CI] 1.79-2.46), parameningeal tumour site (OR 1.83; 95% CI 1.60-2.17) and embryonal RMS histology (OR 1.49; 95% CI 1.19-1.90). CONCLUSIONS: Radiotherapy used for the treatment of HNRMS confers a significant risk of the development of pituitary dysfunction. AMORE-based treatment in children with HNRMS resulted in less pituitary dysfunction than treatment with conventional EBRT. Our findings underscore the importance of routine early endocrine follow-up in this specific population.

Undetected episodes of prolonged apnea and severe bradycardia in preterm infants.

Twenty-four-hour tape recordings of ECG and breathing movement were made on 14 preterm infants with prolonged apneic episodes. Despite apnea monitoring systems, 136/203 (67%) apneic episodes greater than or equal to 20 seconds in duration, including 19 episodes greater than or equal to 50 seconds in duration, were not recorded by nursing staff. Of 120 apneic episodes greater than or equal to 30 seconds, 100 (89%) were accompanied by bradycardia less than or equal to 100 beats per minute. Episodes of more marked bradycardia (less than or equal to 80 beats per minute and up to seven minutes in duration) occurred without cessation of breathing movement in 10/14 infants studied. Treatment with theophylline or aminophylline was associated with a reduction in the number of episodes of apnea greater than or equal to 20 seconds accompanied by bradycardia less than or equal to 80 beats per minute (P less than .001). Many prolonged episodes of apnea and bradycardia are going unnoticed in neonatal intensive care units. Further studies are required to investigate and overcome the causes of these failures.

Hyperphenylalaninemia with defective transamination.

Blood phenylalanine concentrations in a female neonate increased slowly to a level at which dietary phenylalanine restriction became necessary. At this point the patient's urinary aromatic acid excretion profile showed only minimal amounts of phenylpyruvic acid or related aromatic acids. Phenylalanine-tolerance tests, and a subsequent challenge with a normal diet for three days, revealed a progressive decline in the blood phenylalanine concentration at which transamination started to occur. This fits the classification of 'hyperphenylalaninemia with transamination defect'. Possible explanations for the defective metabolism are discussed in the light of the experimental findings.

Outcome of preterm infants who suffered neonatal apnoeic attacks.

Thirty infants of less than 31 weeks post-menstrual age were monitored for apnoea using routine medical equipment and intermittent 24-h pneumocardiograms. These infants were examined again between 16 and 36 months of age. Full physical and ophthalmological examinations were carried out as well as audiometry and assessment using the Griffiths mental developmental scales. Twenty-five of these infants had suffered apnoeic attacks and two of these infants had an abnormal developmental quotient. Neither sensorineural deafness of retinopathy of prematurity were detected in the children who suffered apnoeic episodes. The poor prognosis which has been associated with neonatal apnoea may not apply to those infants without other serious neonatal problem.

Does anthracycline administration by infusion in children affect late cardiotoxicity?

The severity of late cardiotoxicity after anthracycline treatment for childhood cancer relates mainly to the cumulative anthracycline dose received, but all dose ranges cause some cardiac dysfunction. Anthracycline administration by infusion in order to lower peak drug concentration has been used in an attempt to reduce cardiotoxicity. Cardiac performance was assessed by echocardiography in children who were relapse-free survivors of treatment for acute lymphoblastic leukaemia (ALL). They received the same cumulative anthracycline dose (daunorubicin 180 mg/m2) either by bolus injection (UKALL X protocol, n = 40) or by infusion (UKALL XI protocol, n = 71) with a follow-up duration of 5.3 +/- 2.0 and 5.4 +/- 1.0 years respectively. On analysis, both the bolus administration and infusion groups showed similar mild impairment of cardiac performance, characterized by increased left ventricular end systolic stress and impaired left ventricular function. In conclusion, subclinical abnormality of left ventricular performance was confirmed in both groups despite the relatively modest cumulative anthracycline dose received. We were unable to demonstrate an advantage of anthracycline administration by 6-h infusion with respect to late cardiotoxicity at this dose.

Prognosis of Down's syndrome with acute leukaemia.

The outcome in children with acute leukaemia with (n = 90) and without Down's syndrome (n = 4377) was compared. Sixty three (70%) of those with Down's syndrome had acute lymphoblastic leukaemia and in comparison with 3664 (84%) controls had similar prognostic features except for a significant excess of the 'common' immunological subtype of acute lymphoblastic leukaemia. The outcome of the children with Down's syndrome was significantly worse with a five year overall actuarial survival of 28% compared with 59% in the control group. It appeared that both suboptimal chemotherapy and a high rate of infective problems contributed to the poor survival. Twenty six children with Down's syndrome had acute myeloblastic leukaemia and were significantly younger and had a higher percentage of the megakaryocytic and erythroid subtypes of acute myeloblastic leukaemia than the 713 controls. The outcome was similar in the two groups. It is concluded that the patients with Down's syndrome who develop acute leukaemia should receive standard protocols without modification, but aggressive supportive care is necessary to improve outcome.

Renal size and function after cure of Wilms' tumour.

Now that most patients with Wilms' tumour are cured, it is practicable to study the long-term morbidity of their treatment and use this information to reduce treatment sequelae in the future. In this study we evaluate the size and function of the remaining kidney in 53 survivors of Wilms' tumour with a mean off treatment follow-up of 13 years. There was evidence of renal dysfunction in 17 (32%), including ten (19%) with a low GFR (< 80 ml/min/1.73 m2SA), six (11%) with hypertension and five (9%) with increased urinary albumin excretion. Measurements of renal size showed 'good' renal compensatory hypertrophy in only 55% of patients. 'Good' refers to renal size of more than 2 s.d. above the mean renal length for children with two kidneys. There were no correlations between GFR, renal size, blood pressure, microalbuminuria or type of treatment. However, children less than 24 months at diagnosis and children receiving chemotherapy with radiation doses to remaining kidney of more than 1200 cGy had a worse renal prognosis. Patients whose Wilms' tumour is diagnosed in infancy should have careful long-term follow-up of renal function and size. Older patients may safely be followed up less often, unless their remaining kidney was received > 1200 cGy.

Subarachnoid cyst with hydrocephalus--a complication of mid-trimester amniocentesis.

We report a child with a subarachnoid cyst with hydrocephalus following a mid-trimester amniocentesis. Although fetal trauma is a rare complication, it is important to stress the need to perform amniocentesis under ultrasound control. Children with neurological disease or convulsions of unknown origin in early infancy who are born to mothers who have had mid-trimester amniocentesis should have a CT scan as part of the investigations to exclude this rare but nevertheless important complication.

4S neuroblastoma: the long-term outcome.

BACKGROUND: Stage 4S neuroblastoma is associated with a high rate of spontaneous maturation and involution, with survival rates of 70-90%. There is little long-term follow-up data describing the disease status or late effects. The aim of this study was to assess the clinical outcome and imaging findings in long-term survivors of 4S neuroblastoma. METHODS: The patient population was identified from a single centre over 26 years. Twenty-five of 31 consecutive patients were long-term survivors. Five died from disease progression and one from cerebral palsy related complications. All survivors underwent clinical examination. Abdominal ultrasound scanning, liver function tests, hepatitis viral screen, and urinary catecholamines were performed. RESULTS: The mean age at diagnosis was 8 +/- 9 weeks with a mean age when studied of 11 years and 10 months +/- 8 years. Twenty of 25 had no significant clinical findings, three had disease associated clinical abnormalities (neurological, multiple subcutaneous nodules). Three patients had treatment related effects (small testes, urethral stricture, radiation induced soft tissue hypoplasia, post-surgical Horners syndrome). Persistant adrenal enlargement and calcification was noted in three patients. Twelve patients had abnormal liver ultrasound findings ranging from mildly coarse echotexture to structural changes without evidence of hepatic dysfunction or infection. Treatment did not correlate with abnormal hepatic ultrasound findings. CONCLUSIONS: The majority of long-term survivors of stage 4S neuroblastoma have no clinically or radiologically significant sequelae but do have residual abnormalities. These findings have implications for subsequent management of unrelated medical conditions in this patient group.