Dermot Murphy

Introduction : Advancements in the treatment of paediatric cancer in recent years, have led to significant improvements in survival. Despite this there is still a significant proportion of patients whose disease; progress despite treatment or recurs after treatment. The factors which determine survival in patients with progressive or recurrent disease are unclear at present. The aim of this study was to investigate the factors which determine prognosis in cases of recurrent or progressive paediatric cancer. Methods : All patients with a diagnosis of solid or CNS tumour, treated at Yorkhill hospital Glasgow between January 1 st 1999 and December 31 st 2009 were evaluated for this study. Of the 339 patients 124 had progressive or recurrent disease. 96 of the 124 cases had data available for analysis. Log rank testing was used to compare survival amongst different types of tumour. Multivariate cox proportional hazard tests were used to model the influence on risk of death of the investigated prognostic factors. Results : 52% of patients were female, 55% had solid tumour. 76 deaths occurred during follow up, all of which were cancer related. 76% of deaths occurred within a year of progression or recurrence and median overall survival time was 240 days. There were significant differences in the survival of different tumour types at initial diagnosis (p=0.048). The treatment patients received after progression or recurrence and the interval from completion of treatment to progression or recurrence were associated with risk of death (p<0.0005 and p=0.029 respectively). Conclusion : Patients with progressive or recurrent paediatric solid and CNS tumour have a poor prognosis. Initial tumour type, interval from completion of treatment to progression or recurrence and treatment; influence prognosis in this group of patients.

Legislative change to cannabis use has generated significant interest into the therapeutic utility of cannabis-derived medical products, particularly in the field of oncology. However, much of this research has focused on adults, leaving physicians and caregivers uncertain as to the safety and efficacy of cannabinoids amongst the pediatric demographic. To this end, the aim of this review is to examine the scope of pharmaceutical cannabis in treatment of pediatric cancer, evaluating its utility as an anti-cancer therapeutic as well as symptom relief agent. This systematic review was conducted following the PRISMA guidelines. 30 included articles comprised of 16 clinical and 14 preclinical studies. There is reasonable evidence to support the use of cannabis in CINV, with plausible utility for other facets of symptomatic relief. Preclinical pediatric cancer models, investigating anti-cancer cannabinoid effect, have provided evidence that may warrant first phase clinical trials.

Secondary and tertiary paediatric services in Scotland are based in large conurbations. Patients often live a great distance from their primary place of care. The Scottish population (5,094,000) is predominantly urban, with over 70% living in ‘The Central Belt’ which encompasses the Forth and Clyde valleys between Edinburgh and Glasgow. A further 20% live around the …

Pediatric renal cell carcinoma (RCC) is a rare type of kidney cancer, most commonly occurring in teenagers and young adolescents. Few relatively large series of pediatric RCC have been reported. Knowledge of clinical characteristics, outcome and treatment strategies are often based on the more frequently occurring adult types of RCC. However, published pediatric data suggest that clinical, molecular and histological characteristics of pediatric RCC differ from adult RCC. This paper summarizes reported series consisting of ≥10 RCC pediatric patients in order to create an up-to-date overview of the clinical and histopathological characteristics, treatment and outcome of pediatric RCC patients.

This study (NCT01288573) investigated plerixafor’s safety and efficacy in children with cancer. Stage 1 investigated the dosage, pharmacokinetics (PK), pharmacodynamics (PD), and safety of plerixafor + standard mobilization (G-CSF ± chemotherapy). The stage 2 primary endpoint was successful mobilization (doubling of peripheral blood CD34+ cell count in the 24 h prior to first apheresis) in patients treated with plerixafor + standard mobilization vs. standard mobilization alone. In stage 1, three patients per age group (2–<6, 6–<12, and 12–<18 years) were treated at each dose level (160, 240, and 320 µg/kg). Based on PK and PD data, the dose proposed for stage 2 was 240 µg/kg (patients 1–<18 years), in which 45 patients were enrolled (30 plerixafor arm, 15 standard arm). Patient demographics and characteristics were well balanced across treatment arms. More patients in the plerixafor arm (24/30, 80%) met the primary endpoint of successful mobilization than in the standard...

TPS10082 Background: Current therapy for relapsed/refractory high-risk neuroblastoma is not evidence based and long-term disease control is poor. Advances in frontline therapy have been achieved through randomised clinical trials. BEACON-Neuroblastoma trial is designed to identify a backbone chemotherapy regimen to be combined with targeted agents and determine if inhibiting angiogenesis with bevacizumab(B) adds to the activity of chemotherapy. It is the first randomized European study for refractory/relapsed neuroblastoma Methods: BEACON-Neuroblastoma is a factorial phase 2, multicentre, international, randomized clinical trial (EudraCT 2012-000072-42, sponsored by the University of Birmingham). Patients 1-21 years with relapsed/refractory high-risk neuroblastoma are randomised to 1 of 4 arms: T (temozolomide), IT (irinotecan-temozolomide), BT (B-T) or BIT (B-IT). The trial tests whether B added to chemotherapy (T or IT) demonstrates activity and whether the addition of I to T increases activity. Primary...

13-cis-retinoic acid is an established component of treatment for children with high-risk neuroblastoma. However, significant hypercalcemia is increasingly recognized as a potentially life-threatening dosage-related side effect. We present 2 patients with significant hypercalcemia secondary to 13-cis-retinoic acid and their management, and identified the predictive factors for susceptibility to hypercalcemia. Assessing glomerular filtration rate and concomitant medication help predict individual susceptibility to hypercalcemia. Calcium levels should be monitored at days 1, 7, and 14 of each course of retinoic acid. An algorithm for the management of hypercalcemia during the affected and subsequent cycles of retinoid therapy is proposed.

Three children presenting with pain in the arm and variable neurological signs are described. Each child had several hospital visits before being accurately diagnosed with a soft-tissue sarcoma in the axillary fossa. All presented with increasing pain at rest or on shoulder movement, and with some evidence of neurological dysfunction in the upper limb. Two of the girls had unremitting night pain. Delays in diagnosis of sarcomas are common despite internationally agreed referral guidelines, which are readily accessible. In children with unusual upper limb neurological symptoms, it is essential to have a high index of suspicion, and examine the arm including the axilla, thoroughly, and refer them early for a specialist opinion.

Three children presenting with pain in the arm and variable neurological signs are described. Each child had several hospital visits before being accurately diagnosed with a soft-tissue sarcoma in the axillary fossa. All presented with increasing pain at rest or on shoulder movement, and with some evidence of neurological dysfunction in the upper limb. Two of the girls had unremitting night pain. Delays in diagnosis of sarcomas are common despite internationally agreed referral guidelines, which are readily accessible. In children with unusual upper limb neurological symptoms, it is essential to have a high index of suspicion, and examine the arm including the axilla, thoroughly, and refer them early for a specialist opinion.

Our aim in this prospective, randomized, double-blinded study was to compare the analgesic effectiveness and side effects of epidural infusions with ropivacaine 2 mg/mL alone (Group R; n = 60) and in combination with fentanyl 1 microg/mL (R1F; n = 59), 2 microg/mL (R2F; n = 62), and 4 microg/mL (R4F; n = 63) for up to 72 h after major abdominal surgery. Effective epidural neural blockade was established before surgery; postoperatively, the infusion rate was titrated to a maximum of 14 mL/h for analgesia. No additional analgesics other than acetaminophen were permitted during the infusion. The median of individual visual analog scale score with coughing were <20 mm for all groups (0 = no pain, 100 = worst pain) and was significantly lower (P < 0.01) for Group R4F at rest and with coughing (compared with Group R). Infusions were discontinued due to inability to control pain in significantly fewer patients in Group R4F (16%) than the other groups (34% to 39%; P < 0.01). For all groups, >90% of patients had no detectable motor block after 24 h. Hypotension, nausea, and pruritus were more common with the larger dose of fentanyl. We conclude that, after major abdominal surgery, an epidural infusion of ropivacaine 2 mg/mL with fentanyl 4 microg/mL provided significantly more effective pain relief over a 3-day period than ropivacaine alone or ropivacaine with lower concentrations of fentanyl. Postoperative epidural analgesic infusions are widely used, but there is little information regarding optimal strengths of opioid with local anesthetic. In this blinded, prospective study, we compared four different epidural infusion solutions for efficacy and side effects over a clinically useful postoperative period and conclude that an epidural infusion of ropivacaine 2 mg/mL with fentanyl 4 microg/mL was most effective.

Administration of the most appropriate dose of chemotherapy to neonates is particularly challenging and frequently not standardised based on any scientific rationale. We report the clinical utility of carboplatin therapeutic drug monitoring in preterm and full-term neonates within the first month of life. Carboplatin therapeutic monitoring was performed to achieve target drug exposures area under the plasma concentration-time curve (AUC values) in nine preterm and full-term neonates diagnosed with retinoblastoma or neuroblastoma treated over an 8year period. Carboplatin was administered over 3days with therapeutic drug monitoring utilised to target cumulative AUC values of 5.2-7.8mg/mlmin. AUC values achieved were within 15% of target values for the individual courses of treatment in all but one patient (12/13 courses of treatment), with dose modifications of up to 215% required to achieve target AUC values, based on initial mg/kg dosing schedules. Carboplatin clearance determined across three consecutive chemotherapy courses in two patients increased from 3.4 to 7.1ml/min and from 7.2 to 16.5ml/min, representing increases of 210-230% over several weeks of treatment. Complete remission was observed in 8/9 patients, with no renal toxicity reported and only one patient experiencing ototoxicity. The study highlights the benefits of utilising therapeutic drug monitoring to achieve target carboplatin AUC values in preterm and full-term neonates treated within the first few weeks of life, particularly in view of marked increases in drug clearance observed over consecutive chemotherapy courses. In the absence of therapeutic drug monitoring, body-weight based dosing is recommended, with dosing guidance provided for both approaches to inform future treatment.

To review the presentation and outcome of patients with Langerhans cell histiocytosis attending The Royal Hospital for Sick Children, Glasgow over a 23-year period. Thirty-one children were diagnosed with Langerhans cell histiocytosis between January 1990 and December 2012. Retrospective information from medical records was gathered on age at diagnosis, presenting symptoms, classification of disease, treatment and long-term outcome. There were 17 boys and 14 girls; median age at diagnosis 2 years 9 months (interquartile range: 1 year 6 months to 4 years 4 months). Eleven were below 2 years and two were below 6 months of age at diagnosis. Eighteen (58%) children had single system disease of which four were multifocal; 13 (42%) had multisystem disease. Seventeen children improved with conservative treatment. Fourteen required steroids and dual agent chemotherapy; three required further chemotherapy. One child died. Two children had successfully treated relapses. Ten developed diabetes...

The use of laparoscopic peritoneal lavage in conjunction with parenteral fluids and antibiotic therapy in the management of generalized peritonitis secondary to perforated diverticular disease of the colon was assessed. This cohort comprised 8 patients with generalized peritonitis secondary to perforated diverticular disease of the left colon that was diagnosed laparoscopically. All the patients had purulent peritonitis, but no fecal contamination. They were treated with laparoscopic peritoneal lavage and intravenous fluids and antibiotics. All patients made a complete recovery, with resumption of normal diet within 5 to 8 days. No patient has required surgical intervention during a 12- to 48-month follow-up. This approach merits further assessment as an alternative to the traditional open surgical management.

A 6-year-old boy with skin lesions suggestive of neurofibromatosis developed a frontotemporal primitive neuroectodermal tumor and was subsequently treated with surgery, craniospinal irradiation, and chemotherapy. After the sixth cycle of treatment with vincristine sulfate, 9 months after diagnosis, the child developed a rapidly progressive bilateral deterioration in visual acuity. Retinal appearances were consistent with optic neuropathy. Gene studies for neurocutaneous syndromes were negative. Brain imaging at this time showed no tumor progression, and in the absence of other etiologies, we implicate vincristine as a probable cause. Discontinuation of this particular agent has allowed bilateral improvement in visual acuity.

Neuroblastoma is the most common extracranial solid tumour in childhood (8% of all childhood cancers), the most frequently diagnosed in infancy, and has one of the highest death rates, while chromaffin tumours rarely present in childhood. Both tumour types produce catecholamines and their metabolites. It is difficult to produce reference ranges for tests in children, and currently, no age-related medical decision limits for free metadrenalines (free metanephrines) in random urine specimens exist in the paediatric literature. Results of vanillylmandelic acid (VMA), 5-hydroxyindoleacetic acid, homovanillic acid (HVA), noradrenaline (NA), adrenaline, dopamine (DA), free normetadrenaline (fNMA), free metadrenaline and free 3-methoxytyramine (f3MT) in 1658 random urines obtained from infants, children and young adults were measured by high performance liquid chromatography with electrochemical detection. Specimens were excluded from consideration if obtained from the following categories, i.e. (a) harbouring neuroblastic, chromaffin, carcinoid or other tumours or malignancies; (b) medical conditions having known association with excess catecholamine excretion; (c) patients administered catecholamine or paracetamol; (d) overly dilute urine; and (e) manifesting outlying values following visual inspection. There remained 872 specimens that were grouped into seven age ranges (<1; 1 or 2; 3 or 4; 5-7; 8-10; 11-13; 14-19 y) for which medical decision limits were determined for each analyte. There was no significant difference between the results for boys or girls. In 55 patients harbouring neuroblastic tumours, HVA (54/55), f3MT (14/16), VMA (45/53) and DA (43/53) were the most frequently elevated analytes at time of diagnosis. In 11 patients presenting in childhood with chromaffin tumours, fNMA (11/11) followed by NA (10/11) were the most frequently elevated. Discussion The likely reasons for outlying or missing values, together with the reasons for variation in the distinctive biochemical patterns of analytes exhibited in individuals harbouring either neuroblastic or chromaffin tumours are discussed.

Our aim in this prospective, randomized, double-blinded study was to compare the analgesic effectiveness and side effects of epidural infusions with ropivacaine 2 mg/mL alone (Group R; n = 60) and in combination with fentanyl 1 microg/mL (R1F; n = 59), 2 microg/mL (R2F; n = 62), and 4 microg/mL (R4F; n = 63) for up to 72 h after major abdominal surgery. Effective epidural neural blockade was established before surgery; postoperatively, the infusion rate was titrated to a maximum of 14 mL/h for analgesia. No additional analgesics other than acetaminophen were permitted during the infusion. The median of individual visual analog scale score with coughing were <20 mm for all groups (0 = no pain, 100 = worst pain) and was significantly lower (P < 0.01) for Group R4F at rest and with coughing (compared with Group R). Infusions were discontinued due to inability to control pain in significantly fewer patients in Group R4F (16%) than the other groups (34% to 39%; P < 0.01). For all groups, >90% of patients had no detectable motor block after 24 h. Hypotension, nausea, and pruritus were more common with the larger dose of fentanyl. We conclude that, after major abdominal surgery, an epidural infusion of ropivacaine 2 mg/mL with fentanyl 4 microg/mL provided significantly more effective pain relief over a 3-day period than ropivacaine alone or ropivacaine with lower concentrations of fentanyl. Postoperative epidural analgesic infusions are widely used, but there is little information regarding optimal strengths of opioid with local anesthetic. In this blinded, prospective study, we compared four different epidural infusion solutions for efficacy and side effects over a clinically useful postoperative period and conclude that an epidural infusion of ropivacaine 2 mg/mL with fentanyl 4 microg/mL was most effective.