Orbital rhabdomyosarcoma: multidisciplinary treatment experience.

Orbital rhabdomyosarcoma (RMS) accounts for 10% of childhood RMS and has a relatively good prognosis of up to 85% 5-year survival. Improved survival has led to increased interest in late effects of treatment. The objective of this study was to review the results of treating orbital RMS with multidisciplinary treatment at Women's and Children's Hospital and Royal Adelaide Hospital with emphasis on late effects of treatment. A retrospective review was carried out of all patients with orbital RMS treated with multidisciplinary treatment including radiation therapy and chemotherapy in the two institutions between 1982 and 2002. A total of five patients (age range 5.5-12 years) satisfied the eligibility requirements. Late effects were significant and included facial bone hypoplasia, cataract formation and growth hormone deficiency. Overall survival was 80% (4/5) with mean follow up of 8 years (range 3-13 years). Given the high cure rates achieved, future treatments must aim to maintain the good results but to reduce the high incidence of late effects of treatment. Standardised rating of late toxicity, long-term follow-up clinics, and implementation of modern radiation techniques (3-D conformal radiotherapy, intensity modulated radiotherapy, proton therapy) for patients with orbital RMS are important to improving outcome.

Allogeneic bone marrow transplant improves outcome for juvenile myelomonocytic leukaemia.

OBJECTIVE: To correlate clinical presentation and therapeutic outcomes in children with a diagnosis of juvenile myelomonocytic leukaemia. METHODS: The medical records of 14 children who fulfilled the International Juvenile Myelomonocytic Leukaemia Working Group Criteria for a diagnosis of juvenile myelomonocytic leukaemia (JMML) presenting to a single institution were reviewed, and their clinical status at September 2000 was documented. RESULTS: The most common presenting features were hepatosplenomegaly and lymphadenopathy. Fifty per cent of cases presented in the first year of life. Nine of 14 patients initially received chemotherapy otherwise used in the treatment of acute myeloid or lymphoblastic leukaemia with no apparent benefit. All six patients who received conditioning therapy with chemotherapy alone, followed by allogeneic bone marrow transplant (BMT), are in complete remission at a median follow-up duration of 12 months (range 5-91 months). Five of six patients surviving post-allogeneic BMT received marrow from an unrelated donor. Only one of seven patients who did not receive BMT survived long-term. CONCLUSION: Children with a diagnosis of JMML should be treated with allogeneic BMT as soon as a suitable donor is found. The role of anti-leukaemic therapy in this disease, prior to BMT, requires further investigation in the context of a multicentre clinical trial.

Pseudomonas aeruginosa infection mimicking erythema annulare centrifugum.

A 3-year-old girl receiving chemotherapy for acute lymphocytic leukaemia developed a rapidly expanding red annular plaque on her thigh, initially without signs of systemic toxicity or local pain. Subsequently she developed Pseudomonas aeruginosa sepsis and purpura at the leading edge of the plaque. Skin biopsy showed an extensive necrotizing vasculitis with numerous Gram-negative bacilli in the blood vessel walls. In immunocompromised individuals, skin biopsy and culture of cutaneous lesions for bacteria and fungi should be considered even in the absence of signs of systemic toxicity or multiple lesions.

Bones, groans and blasts.

A 14-year-old girl presented with the acute onset of gastrointestinal symptoms due to hypercalcaemia. Chest X-ray revealed osteolytic lesions in the ribs which in conjunction with a normal parathyroid hormone level raised the possibility of malignancy. Despite the absence of blast cells in her blood film, the bone marrow biopsy was diagnostic of acute lymphoblastic leukaemia. She responded well to treatment with pamidronate and chemotherapy.

Pediatric heparin-induced thrombocytopenia: management with Danaparoid (orgaran).

Heparin-induced thrombocytopenia is a rare and serious complication of anticoagulation therapy. There remains a paucity of information pertaining to alternative anticoagulation strategies for use during cardiopulmonary bypass concomitant with heparin-induced thrombocytopenia, especially in children. We report the successful treatment of heparin-induced thrombocytopenia and subsequent hemorrhagic complications postoperatively in a 2-year-old child with Danaparoid (orgaran). Emergent conduit revision with cardiopulmonary bypass was required for a thrombosed systemic-venous to pulmonary-arterial connection (completion modified Fontan procedure). Required doses of Danaparoid were consistently twofold that previously reported for adults.

Reticulated platelet counts in the diagnosis of acute immune thrombocytopenic purpura.

PURPOSE: Bone marrow aspiration is often performed to diagnose childhood acute immune thrombocytopenic purpura (ITP) because no non-invasive investigation to confirm the diagnosis is routinely available. Reticulated platelets (RPs--young platelets characterized by a high RNA content--increase with increased platelet production and may be useful in the diagnosis of ITP. METHODS: To assess the role of RP counts in distinguishing ITP, we compared counts from 15 consecutive patients with ITP with counts from 20 patients with acute lymphoblastic leukemia (ALL), 10 with aplasia, and 27 healthy normal children. Whole blood in edetic acid (EDTA) was labelled with a platelet-specific monoclonal antibody and incubated with thiazole orange (TO). A standard gate was set to achieve a fluorescence value of 1.3 +/- 0.5% for control lyophilized platelets. RESULTS: Patients with ITP had a mean (+/- 1 standard deviation) RP level of 32.9 +/- 10.2%; patients with ALL, 6.6 +/- 3.1%; patients with aplasia, 3.4 +/- 2.0%; and normal patients, 7.9 +/- 2.9%. The difference in RPs between the ITP group and the ALL, aplasia, and normal groups was highly significant (p < 0.0001 each), with no significant difference between the non-ITP groups (p = 0.12). CONCLUSIONS: Measuring RPs by this simple whole-blood cytometric technique discriminated very well between the acute ITP and non-ITP groups. This test has a strong positive predictive value and may prove very useful in the assessment of childhood acute ITP and the screening of candidates for bone marrow aspiration.

Cellular expression of adhesion factors in childhood rhabdomyosarcoma.

Tumor invasion and metastasis are believed to involve the adhesive interaction of tumor cells with extracellular matrix (ECM). This study reports the expression of laminin, fibronectin, thrombospondin, tenascin, and CD44 in rhabdomyosarcoma cells taken from tumors derived from 12 pediatric patients. Twelve paraffin-embedded rhabdomyosarcomas consisting of five alveolar, six embryonal, and one botryoid subtype were examined. All tumors demonstrated positive staining for tenascin and thrombospondin, 10 were positive for fibronectin, 5 positive for laminin, and 4 positive for CD44. Both specimens without cellular staining for fibronectin were of embryonal subtype and no alveolar rhabdomyosarcomas were positive for CD44. No association of the expression of the studied ECM proteins and receptor with the presence of metastatic disease at clinical presentation or with the level of tumor differentiation was found.

Comparative activity of cefepime, alone and in combination, against clinical isolates of Pseudomonas aeruginosa and Pseudomonas cepacia from cystic fibrosis patients.

The comparative in vitro activity and synergy of cefepime were evaluated with clinical isolates of Pseudomonas aeruginosa and Pseudomonas cepacia from cystic fibrosis patients. The activity of cefepime, both alone and in combination, was comparable to those of other antibiotics. The clinical efficacy of cefepime in cystic fibrosis patients merits investigation.

In vitro activities of combinations of aztreonam, ciprofloxacin, and ceftazidime against clinical isolates of Pseudomonas aeruginosa and Pseudomonas cepacia from patients with cystic fibrosis.

The in vitro activities of two-drug combinations of aztreonam, ciprofloxacin, and ceftazidime were studied in 96 clinical isolates of Pseudomonas aeruginosa and in 20 clinical isolates of Pseudomonas cepacia from cystic fibrosis patients. Some synergy was observed with each combination used against P. aeruginosa, but synergy was rare when the combinations were used against P. cepacia.

In vitro activity of aztreonam combined with tobramycin and gentamicin against clinical isolates of Pseudomonas aeruginosa and Pseudomonas cepacia from patients with cystic fibrosis.

The in vitro activity of aztreonam combined with tobramycin and with gentamicin was assessed in 78 clinical isolates of Pseudomonas aeruginosa and 11 clinical isolates of Pseudomonas cepacia from patients with cystic fibrosis. Synergy was detected in 56.4% of P. aeruginosa isolates and 60% of P. cepacia isolates with the aztreonam-tobramycin combination and in 49.3% of P. aeruginosa isolates and 81.8% of P. cepacia isolates with the aztreonam-gentamicin combination. No antagonism was observed. These combinations merit clinical evaluation in the treatment of patients with cystic fibrosis.

Absence of rapidly developing resistance during treatment of cystic fibrosis patients with aztreonam.

The in vitro activity of aztreonam and 10 other antibiotics was determined for clinical isolates of Pseudomonas aeruginosa from 18 cystic fibrosis patients obtained before, at the end of, and 7-14 days after the completion of therapy with aztreonam. The percent of isolates susceptible to aztreonam at each sampling period were 79%, 78%, and 81% respectively.

Azlocillin pharmacokinetics in patients with cystic fibrosis.

The pharmacokinetics of azlocillin were studied in 10 cystic fibrosis patients, ranging in age from 11 to 28 years. The patients received a 9- to 23-day course of 350 mg of azlocillin per kg in four or six divided daily doses in combination with am aminoglycoside. Blood and urine samples were collected at specified times after the last dose of the course of azlocillin therapy and then assayed for azlocillin content. Pharmacokinetic parameters were determined by noncompartmental analysis. Mean values for serum half-life (1.74 h), disposition constant (0.41 h-1), total body clearance (123 ml/kg per h), and renal clearance (58 ml/kg per h) were determined. All patients exhibited improvement with respect to clinical and laboratory parameters and displayed no adverse reactions. The pharmacokinetic analysis offers further evidence of the dose-dependent nature of azlocillin elimination, but elimination did not appear to be altered in cystic fibrosis patients.

Piperacillin distribution into bile, gallbladder wall, abdominal skeletal muscle, and adipose tissue in surgical patients.

The concentrations of piperacillin in serum, bile, gallbladder wall, abdominal skeletal muscle, and adipose tissue were measured simultaneously at various times after the intravenous administration of a single 5-g dose to each of 14 patients undergoing biliary tract surgery. Piperacillin concentrated in the bile with peak levels exceeding 4,000 micrograms/ml. In a single patient with cystic duct obstruction, trace gallbladder bile piperacillin levels were measured. Gallbladder wall concentrations of piperacillin tended to be higher than corresponding serum concentrations, with a correlation observed between tissue values and the degree of acute gallbladder inflammation and gallbladder bile piperacillin concentrations. Mean peak muscle and adipose tissue piperacillin concentrations of 31 and 27 micrograms/g, respectively, were reached at between 2 and 3 h after the start of infusion. These concentrations exceeded the minimum inhibitory concentration for a majority of susceptible organisms. A single 5-g dose of piperacillin achieved therapeutic levels in gallbladder wall, intraabdominal skeletal muscle, and adipose tissue and concentrated in the bile of patients with patent biliary tracts.