Consensus statement for the treatment of infantile haemangiomas with propranolol.

Although most infantile haemangiomas do not require treatment due to a natural history of spontaneous involution, some require early intervention. The Australasian Vascular Anomalies Network and the Australasian Paediatric Dermatology Network have developed a consensus statement for the treatment of infantile haemangiomas with oral propranolol. Infants with haemangiomas that are life threatening, at risk of ulceration, or at risk of causing a significant functional impairment, psychological impact or physical deformity should be treated early with oral propranolol. Oral propranolol is safe and effective and in most healthy infants oral propranolol can be started in an outpatient setting.

Bilateral Wilms tumor and early presentation in pediatric patients is associated with the truncation of the Wilms tumor 1 protein.

OBJECTIVES: To investigate the frequency of constitutional Wilms tumor 1 gene (WT1) abnormalities in children with bilateral Wilms tumor (WT) and the age of tumor onset in patients with a mutation. STUDY DESIGN: Eight patients with bilateral WT were studied. High-resolution melting and direct sequencing were used to screen for the WT1 gene. Western blotting was performed to determine whether the identified mutations were associated with expressed truncated WT1 protein. RESULTS: The median age of tumor onset in patients with a mutation in the WT1 was lower (10 months) than in those without a mutation (39 months). Three novel heterozygous nonsense mutations were identified in exon 8 in peripheral blood from 3 individuals, whereas all 3 tumor tissues lacked the wild-type allele. All mutations led to a premature stop codon with truncation of the WT1 protein. In 1 patient, a truncated form of WT1 protein was identified, suggesting that development of the WT may have resulted from expression of an abnormal protein. Four distinct silent single-nucleotide polymorphisms (SNPs) were detected. All 3 patients with a pathogenic WT1 mutation had 2 synonymous SNPs, whereas only 1 of the remaining 5 patients had a single synonymous SNP (P < .05). CONCLUSIONS: Bilateral WT are associated with early presentation in pediatric patients and a high frequency of WT1 nonsense mutations in exon 8. Silent SNPs may also be involved in the development of WT.

Successful treatment of kaposiform hemangioendothelioma and tufted angioma with vincristine.

BACKGROUND: Kaposiform hemangioendothelioma (KHE) and tufted angioma (TA) are rare, locally aggressive vascular tumors. Although currently classified as separate entities, they are becoming increasingly recognized as a spectrum of the same pathology. There is a well-recognized association with Kasabach-Merritt phenomenon KHE and TA are considered neoplasms of intermediate malignancy because of infiltrative growth, local aggressiveness, and variable prognosis. To date, definitive treatment for these vascular tumors has had limited success. AIM: To evaluate the safety, efficacy, and role of vincristine in the treatment of KHE and TA. METHODS: Case review of patient files and pathology reports at The Children's Hospital at Westmead from 1995 to 2009. RESULTS: Twelve cases with KHE or TA were identified. Seven cases were treated with vincristine. The survival rate in the vincristine group was 100%. Mean age of diagnosis was 30 months (range birth to 9 y). 6 patients were female (85.7%). Mean time of the follow-up was 4 years (range 4 mo to 8 y). Out of the 7 cases treated with vincristine, 3 patients had associated Kasabach-Merritt phenomenon (43%). Complete resolution, regression in size, and improvement in analgesia were found in 1 case (14%), 3 cases (43%) and 2 cases (29%), respectively. Vincristine related side effects occurred in 2 cases (29%). CONCLUSIONS: Vincristine is an effective treatment option for KHE/TA. It is associated with a low side effect profile and should be considered as the first-line agent.

Successful treatment of infantile haemangiomas of the orbit with propranolol.

BACKGROUND: Propranolol is a novel therapeutic agent in the treatment of cutaneous infantile haemangiomas. We assessed the effect of propranolol therapy in infantile haemangiomas of the orbit. METHODS: A case series of four patients with orbital infantile haemangiomas were referred for management in our tertiary referral hospitals. Two of the patients had inadequate responses to prior corticosteroid therapy. One of the patients was commenced on propranolol at 2.5 years of age when the lesion was not in the proliferative phase. This represented the first case report of propranolol treatment for infantile haemangioma outside infancy. The other three children were in their infancy when propranolol was commenced. The patients were treated with oral propranolol. RESULTS: All patients had significant improvement in their physical appearance, ocular examination findings and size of their lesions on radiological evaluation. No side-effects of propranolol treatment were observed. CONCLUSIONS: Propranolol is a promising treatment against infantile haemangiomas in the orbit, not only in infants but also in an older child with a stable lesion.

Lung tumours in children.

Primary lung tumours in children are rare and metastatic lung disease is uncommon. The majority of children who present with a primary or secondary pulmonary malignancy will present co-incidentally while seeking attention for another medical problem, or with non-specific abnormalities such as cough with collapse or consolidation on the chest radiograph. With improved techniques of medical imaging for diagnostic and therapeutic purposes and improved outcomes of childhood malignancies, the role of the respiratory paediatrician in the ongoing care of oncology patients is likely to increase.

The impact of Asian descent on the incidence of acquired severe aplastic anaemia in children.

Previous studies have suggested an increased incidence of acquired severe aplastic anaemia in Asian populations. We evaluated the incidence of aplastic anaemia in people of Asian descent, using a well-defined paediatric (0-14 years) population in British Columbia, Canada to minimize environmental factors. The incidence in children of East/South-east Asian descent (6.9/million/year) and South Asian (East Indian) descent (7.3/million/year) was higher than for those of White/mixed ethnic descent (1.7/million/year). There appeared to be no contribution by environmental factors. This study shows that Asian children have an increased incidence of severe aplastic anaemia possibly as a result of a genetic predisposition.

Non-resectable congenital tumors with the ETV6-NTRK3 gene fusion are highly responsive to chemotherapy.

BACKGROUND: Recently, the ETV6-NTRK3 gene fusion has been identified in both infantile fibrosarcoma and cellular mesoblastic nephroma. For both these tumors standard curative treatment has been primarily surgical with wide local excision. This has frequently involved radical and even mutilating surgery. PROCEDURE: This report discusses three infants with congenital tumors, two congenital fibrosarcomas, and one atypical congenital mesoblastic nephroma, not easily amenable to surgical intervention. RESULTS: All three were treated with pre-operative chemotherapy with excellent responses negating the need for amputation in two patients. In each patient, the ETV6-NTRK3 gene fusion was identified by reverse transcriptase-polymerase chain reaction (RT-PCR) in the tumor specimens. CONCLUSIONS: Our findings suggest that the ETV6-NTRK3 gene fusion may underlie the distinctive biological properties of these tumors and may also indicate tumor chemosensitivity. In this group of patients pre-operative chemotherapy may abrogate the need for morbid surgical procedures.