Photobiomodulation with a combination of two wavelengths in the treatment of oral mucositis in children: The PEDIALASE feasibility study.

Photobiomodulation is recommended in adults for the prevention of mucositis induced by cervicofacial irradiation or pre-transplant chemotherapy. The results of pediatric studies are promising but this support treatment is still underused. The objective was to conduct a feasibility study in the pediatric hematology-oncology unit at X Children's Hospital. Extra- and intraoral scans were performed a minimum of three times every 2 days for grade 2 or higher mucositis in children (median age, 8.6 years) using the Oncolase laser (Biophoton, Saint Alban, France), with a combination of two wavelengths (635 and 815nm). The effect of the laser on mucositis grade, pain, the child's tolerance, and the time dedicated to this care were also evaluated. The success of the procedure was 77% in 1 year, with the inclusion of 84% of the patients (n=22) and 146 laser treatment sessions (median of four per episode of mucositis). We observed excellent tolerance and pain relief with a gain of two points on the VAS and the HEDEN mucositis scale. This study shows that photobiomodulation that incorporates two application modes (intra- and extraoral) through the combination of two wavelengths is feasible when integrated into the care of a pediatric hematology-oncology department and is perfectly tolerated, even by young children. Along with oral hygiene and analgesic management, it alleviates pain associated with oral mucositis.

A French retrospective study on clinical outcome in 102 choroid plexus tumors in children.

The aim of this study was to review and describe therapeutic approaches in children with choroid plexus tumor (CPT) based on a nationwide series. The World Health Organization classification subdivides these rare tumors into three histological subtypes corresponding to three grades of malignancy: low grade (grade I) choroid plexus papilloma (CPP), intermediate grade (grade II) atypical choroid plexus papilloma (aCPP) and high grade (grade III) choroid plexus carcinoma (CPC). This retrospective study included 102 French children younger than 18 years, treated from 2000 to 2012: 54 CPP, 26 aCPP and 22 CPC. The 5 year overall survival was 100% in CPP, 96.2% in aCPP and 64.7% in CPC. In patients with localized disease, complete surgical resection was achieved in 48/52 CPP, 20/26 aCPP and 7/14 CPC. In this group, patients with complete surgical resection had better event free survival than patients with partial resection (88.9 vs. 41.6%). 28 patients (1 CPP, 6 aCPP and 22 CPC) had adjuvant chemotherapy. 2 aCPP and 9 CPC had radiotherapy. We underlined the need for a central histological review to accurately analyze clinical data; we reported a much higher overall survival for CPC than in most previous CPT series probably including atypical teratoid rhabdoid tumors. In our series, the 5 years overall survival in CPC (64.7%) was higher than event free survival (25.2%) and could be interpreted as a clue for the efficiency of adjuvant/salvage therapy even if the heterogeneity of applied treatments in this retrospective series does not allow for meaningful statistical comparisons.

Complex regional pain syndrome type I in children. Clinical description and quality of life.

INTRODUCTION: Complex regional pain syndrome type 1 (CRPS I) in children differs from its adult counterpart and relevant literature is scarce. Our aim was to investigate potential risk factors and to assess midterm outcome and quality of life. MATERIAL AND METHODS: Medical records of patients diagnosed with CRPS I between 2004 and 2012 were analyzed. Patients and parents were called for a phone interview including the PEDS Quality of Life 4-0 questionnaire. Results were compared to a control group matched for age, gender and socio-economic status. RESULTS: Seventy-three patients were included (64 girls, 9 boys). Mean age at diagnosis was 11.5 years and mean time to diagnosis was 14.2 months. The lower limb was affected in 89% of cases. Allodynia, coldness and cyanosis were noted in 95%, 81% and of 74% of cases, respectively. Forty-nine percent of patients reported a physical injury. Multivariate analysis showed a strong association with being anxious (OR = 44.9, 95% CI [7.4-273]), presence of an atopic background (OR = 25.0, 95% CI: [4.6-135]), being good to excellent school performers (OR = 8.4 95% CI [1.3-52.1]), and having trouble falling asleep (OR = 5.3, 95% CI [1.6-17.0]). At a mean 37 months' follow-up (12-102), PEDS QL 4-0 score was significantly lower in CRPS patients compared to controls. Fifty-seven percent of patients acknowledged healing and 55% had presented a relapse. CONCLUSION: Childhood onset CRPS I affects predominantly preadolescent girls at the ankle. The present study highlights the relatively poor outcome, especially its physical and emotional aspects and the large role of psychology. LEVEL OF EVIDENCE: IV.

[Study of renal veins by multidetector-row computed tomography scans]. / Étude radiologique des variations anatomiques des veines rénales par scanner multidétecteurs en coupes fines.

PURPOSE: To determine the prevalence of renal vein variants. To investigate the distribution of renal veins. METHODS: We retrospectively reviewed spiral computed tomography (CT) scans of the abdomen performed during a two-month period. The same protocol was used for all CT scans: same multidetector-row CT scanner (Siemens(®)), 1 to 2-mm section thickness, injection of intravenous iomeprol. The study group included 121 patients, aged 21.7 to 93.4 years (mean age 60.9 ± 15.4 years). The sex ratio was 2/1, with 80 men and 41 women. RESULTS: Seventy-three percent of the study group (88 patients) had no variants of the renal veins. Indeed almost 40% (48 patients) had one artery and one vein on each side, with typical course, and 33% (40 patients) had course and/or number variants of the renal arteries. Variants of the right renal vein consisted in multiple veins in 20.6% (25 cases). We detected no case of multiple left renal veins, but we described variations of its course in 9.1% (11 cases): 5 cases of retroaortic left renal vein (4.1%) and 6 cases of circumaortic left renal vein (5%). Three of these 11 patients had an associated double right renal vein. The probability to have a right renal vein variant was significantly higher than a left one (OR = 2.6, P = 0.01). And we found a significantly higher risk of having a venous variant in women (OR = 2.4, P = 0.04). We detected no case of inferior vena cava variant. CONCLUSION: In our study, prevalence of a circum- or retroaortic left renal vein appeared higher than previously reported in the literature (9.1%). Knowledge of anatomical variants of renal vasculature is crucial and this study puts the emphasis on variations of course and number of renal vessels. Those variations are not so uncommon and should be known by radiologists and also by surgeons. Their knowledge has major clinical implications in practice and it contributes to the safety of renal and retroperitoneal surgery.

Treatment of children over the age of one year with unresectable localised neuroblastoma without MYCN amplification: results of the SIOPEN study.

BACKGROUND: In children older than 1 year with localised unresectable neuroblastoma (NB), treatment strategies are heterogeneous according to the national groups. The objective of this phase III non-randomised study was to evaluate the efficacy of conventional chemotherapy followed by surgery. PATIENTS AND METHODS: In the presence of surgical risk factors (SRF), six courses of chemotherapy alternating Carboplatin-Etoposide and Vincristin-Cyclophosphamide-Doxorubicin were given, and surgical resection was attempted after four. Survival analyses were performed using an intention-to-treat approach. The main objective was to achieve a 5-year survival over 80%. RESULTS: Out of 191 registered children, 160 were evaluable. There were 62.5% older than 18 months and 52.5% had unfavourable histology according to International Neuroblastoma Pathology Classification (INPC). Chemotherapy reduced the number of SRFs by one third. Delayed surgery was attempted in 86.3% of patients and was complete or nearly complete in 74%. The 5-year EFS and OS were 76.4% and 87.6% respectively, with significant better results for patients younger than 18 months or with favourable histology. CONCLUSION: This strategy provides encouraging results in children older than 1 year or 12 months with localised unresectable NB without MYCN amplification. However, in children older than 18 months and with unfavourable histology, additional treatment is recommended.

Segmental chromosomal alterations lead to a higher risk of relapse in infants with MYCN-non-amplified localised unresectable/disseminated neuroblastoma (a SIOPEN collaborative study).

BACKGROUND: In neuroblastoma (NB), the presence of segmental chromosome alterations (SCAs) is associated with a higher risk of relapse. METHODS: In order to analyse the role of SCAs in infants with localised unresectable/disseminated NB without MYCN amplification, we have performed an array CGH analysis of tumours from infants enrolled in the prospective European INES trials. RESULTS: Tumour samples from 218 out of 300 enroled patients could be analysed. Segmental chromosome alterations were observed in 11%, 20% and 59% of infants enroled in trials INES99.1 (localised unresectable NB), INES99.2 (stage 4s) and INES99.3 (stage 4) (P<0.0001). Progression-free survival was poorer in patients whose tumours harboured SCA, in the whole population and in trials INES99.1 and INES99.2, in the absence of clinical symptoms (log-rank test, P=0.0001, P=0.04 and P=0.0003, respectively). In multivariate analysis, a SCA genomic profile was the strongest predictor of poorer progression-free survival. CONCLUSION: In infants with stage 4s MYCN-non-amplified NB, a SCA genomic profile identifies patients who will require upfront treatment even in the absence of other clinical indication for therapy, whereas in infants with localised unresectable NB, a genomic profile characterised by the absence of SCA identifies patients in whom treatment reduction might be possible. These findings will be implemented in a future international trial.

Chromosomal CGH identifies patients with a higher risk of relapse in neuroblastoma without MYCN amplification.

Whereas neuroblastoma (NB) with MYCN amplification presents a poor prognosis, no single marker allows to reliably predict outcome in tumours without MYCN amplification. We report here an extensive analysis of 147 NB samples at diagnosis, without MYCN amplification, by chromosomal comparative genomic hybridisation (CGH), providing a comprehensive overview of their genomic imbalances. Comparative genomic hybridisation profiles showed gains or losses of entire chromosomes (type 1) in 71 cases, whereas partial chromosome gains or losses (type 2), including gain involving 17q were observed in 68 cases. Atypical profiles were present in eight cases. A type 1 profile was observed more frequently in localised disease (P<0.0001), and in patients of less than 12 months at diagnosis (P<0.0001). A type 2 genomic profile was associated with a higher risk of relapse in the overall population (log-rank test; P<0.0001), but also in the subgroup of patients with localised disease (log-rank test, P=0.007). In multivariate analysis, the genomic profile was the strongest independent prognostic factor. In conclusion, the genomic profile is of prognostic impact in patients without MYCN amplification, making it a help in the management of low-stage NB. Further studies using higher-resolution CGH are needed to better characterise atypical genomic alterations.

[Neonatal localized neuroblastoma: 52 cases treated from 1990 to 1999]. / Neuroblastomes localisés du nouveau-né: 52 cas traités de 1990 à 1999.

UNLABELLED: Neuroblastoma is the most frequent tumor observed in the newborn. The aim of this study was to review clinical features, treatment and outcome of newborns diagnosed with a localized neuroblastoma. POPULATION AND METHODS: Data from 52 cases treated according to the NBL 90 and 94 protocols between 1990 and 1999 in 18 French centers of pediatric oncology were analyzed. RESULTS: The median age at diagnosis was 12 days (range 0-28) with antenatal detection in 14 patients (27%). Tumor location was abdominal in 40 patients (adrenal in 20 of the 40), thoracic in eight, pelvic in three, and cervical in one. N-myc amplification was observed in one out of 40 evaluable cases. The size of the primary tumor was less than 5 cm in 25 cases, between 5 and 10 cm in 25 and more than 10 cm in two. Dumbbell tumor was observed in seven, of whom five had neurological deficit. One child died from hemorrhage after fine needle biopsy during diagnostic procedure. Primary surgical resection was attempted in 37 infants, of whom two died of surgery related complications and three had nephrectomy. Tumor was deemed as unresectable in 14 patients, and primary chemotherapy was given followed by surgical excision in 12. One of them died a few days after the beginning of chemotherapy. As a whole, continuous complete remission was achieved in 48 children, four of them after relapse. Overall survival was 92% with a median follow-up of 46 months (0-113 months). CONCLUSION: The excellent prognosis of localized NB in neonates needs very restrictive surgical indications, with well-established anatomic and imaging criteria. Indeed, chemotherapy based on weight and managed by expert teams should allow to perform surgical excision in safer conditions for unresectable tumors.

Localized cervical neuroblastoma: prevention of surgical complications.

OBJECTIVES: The purpose of this study focused on cervical neuroblastoma (NB) was to assess the prognosis, define the most suitable methods of investigation, and evaluate risk factors for complications following primary surgery. METHODS: Between 1990 and 1999, we conducted two consecutive prospective multicentric studies (NBL90 and NBL94) on localized NB. Because the first study (1990-1994) found surgery-related morbidity and mortality, several surgical risk factors (i.e. adhesion to major vessels, size, friability, and dumb bell tumor) were defined and used prospectively as criteria of resectability in the second study (1994-1999). RESULTS: Of 617 cases included in the two studies, 43 involved cervical NB including 17 cervicothoracic tumors. With a median follow-up of 4 years, overall survival and event-free survival rates were 91 and 81%, respectively with no significant difference between cervical or cervicothoracic NB. Seventeen patients were included in the second study; surgery was used as the first line treatment in 11. Full pre-operative work-up was performed in eight patients, demonstrating one or more risk factors in three. The remaining three patients underwent emergency surgery with no pre-operative work-up or only ultrasound: two developed serious complications. All three patients presenting documented risk factors developed post-operative complications versus only two of the eight patients who presented no risk factor (n = 5) or were inadequately evaluated (n = 3) (P = 0.06). None of the five patients in whom full work-up demonstrated no risk factor had post-operative complications (P = 0.02). CONCLUSIONS: Cervical neuroblastoma has a favorable prognosis. Surgery is the treatment of choice but there is a risk of complications. Appropriate pre-operative work-up is mandatory to evaluate resectability. The surgical risk factors defined for our second study seem to be significant predictors of post-operative complications.

Localised and unresectable neuroblastoma in infants: excellent outcome with low-dose primary chemotherapy.

The purpose of this study was to evaluate the efficacy of low-dose chemotherapy in infants with localised and unresectable neuroblastoma (NB). All consecutive infants with localised NB and no N-myc amplification were eligible in the SFOP-NBL 94 study. Primary tumour was deemed as unresectable according to imaging data showing any risk of immediate resection. Diagnostic procedures and staging were conducted according to INSS recommendations. For children, provided that they had no threatening symptom (i.e. vital risk or dumb-bell NB with neurologic deficit), chemotherapy consisted in low-dose cyclophosphamide (5 mg(-1)kg day(-1) x 5 days) and vincristine (0.05 mg kg(-1) at day 1)-CV and repeated one to three times every 2 weeks until surgical excision can be safely performed. No postoperative treatment was given. Between January 1995 and December 1999, 134 consecutive infants with localised NB were registered in the study, of whom 39 had an unresectable NB without N-myc amplification. Among them 28 had no threatening symptom and received CV according to the protocol. Objective response was observed in 14 (50%) and the other 14 were given second-line chemotherapy because of no response. Surgery was attempted in 38 patients including 14 after CV alone, leading to complete resection in 23. Relapses occurred in four patients all local. Survival and event-free survival were 100 and 90+/-5% with a median follow-up of 55 months (range 33-93). In conclusion primary low-dose chemotherapy without anthracyclines is efficient in about half of the infants presenting with an unresectable NB and no N-myc amplification, allowing excellent survival rates without jeopardising their long-term outcome even for nonresponding patients who received standard regimen.