Long-term use of peripherally inserted central venous catheters for cancer chemotherapy in children

Background Peripherally inserted central venous catheters (PICCs) have been increasingly used in pediatric patients. However, little is known about the incidence and risk of complications when using this device in children with cancer. The purposes of this study are to assess the feasibility of PICCs and to determine the risk factors for PICC-related complications in pediatric patients with various types of malignancies.Patients and methods We attempted to place PICCs in 53 patients with a median age of 5 years ranging from 2 months to 20 years. PICCs were used to administer fluid, parenteral nutrition, anticancer agents, antibiotics, and blood products and also for the through-line blood sampling. The duration of catheterization and the incidence of PICC-related complications requiring removal were retrospectively evaluated in association with the diagnosis, sex, age and body weight of the patients, size, insertion site and tip location of the catheters, type of treatment, and duration of leukopenia.Results PICCs were successfully placed in 109 of 112 attempts (97.3%) in 53 patients, and they were followed for a total of 11,797 catheter days (median placement, 87 days; range, 3 to 512 days). Fifty five PICCs (50.5%) were removed as a result of PICC-related complications with a rate of 4.66 per 1,000 catheter days. The most common reasons for catheter removal were occlusion (n=18), breakage/leakage (15), and infection (10). More than 70% of such complications occurred more than 30 days after placement. The catheter tip location in the superior vena cava or the right atrium might decrease the risk of complications. Other parameters did not influence the incidence of complications.Conclusions PICCs were found to provide a reliable access for prolonged intravenous administration and blood sampling in children intensively treated for hematologic and solid malignancies, thus leading to a reduction of physical pain and psychological stress in such patients. However, the long-term placement of PICCs may also be related to an increased risk of complications.     

Genetic susceptibility to Kawasaki disease: analysis of pattern recognition receptor genes

Kawasaki disease (KD) is a systemic vasculitis of unknown etiology occurring in infants and children. Several lines of evidence suggested the importance of genetic factors and infectious triggers for the pathogenesis of KD. We have reported that oral administration of a pure NOD1 ligand induces coronary arteritis in mice without fail. Since NOD1 is one of the pattern recognition receptors (PRRs) which play important roles in the innate immunity for the detection of microbial substances and induce inflammatory responses, we have investigated the association of PRR genes with the development of KD. Forty-six tagging-SNPs in 19 PRR genes were genotyped in Japanese KD patients (n=356, consisting of two groups) and controls (n=215). The genotypes and allele frequencies of each SNP or haplotype were compared between KD patients and controls. As a result, we did not find any genes with strongly contributed to the development of KD. A haplotype, G-T-C-C, in the NOD1 gene, was associated with lower risk for KD development (KD 1st group versus controls: 23.2% versus 35.3%, Pc=0.0385). The second-round case-control study in KD group 2 demonstrated that a haplotype, T-T-C-G-A-C, in the NLRP1 gene was associated with a higher risk for KD development (4.9% versus 1.2%, Pc=0.035). From the association analysis of SNPs and haplotypes of 19 PRR genes, NOD1 and NLRP1 seemed to partly contribute to the development of KD. Further analysis with larger samples of another independent set would be needed to find confirmative results.     

Unrelated donor cord blood transplantation for childhood severe aplastic anemia after a modified conditioning

Treatment of severe aplastic anemia (SAA) patients who lack human leukocyte antigen (HLA)-matched donors and failed immunosuppressive therapy (IST) is challenging. Recently, umbilical cord blood transplantation (CBT) after non-myeloablative therapy has been reported in adult but not in childhood SAA. However, most cases resulted in mixed donor chimerism and incomplete hematological recovery. We reported an 11-yr-old girl with recurred SAA 5 yr after IST who underwent unrelated donor CBT after a modified regimen. This patient had renal and cardiac dysfunction, and lacked suitable bone marrow donors. The 3.9 x 10(7)/kg CB cells from an HLA one-locus mismatched unrelated donor were infused after conditioning with total body irradiation (5 Gy), melphalan (120 mg/m(2)), and fludarabin (120 mg/m(2)). Hematological recovery was favorable in complete chimerism. A major complication was only skin graft-versus-host disease (grade I). CB could be an alternate stem cell source for childhood SAA after modified preparative regimen.     

Fbxw7 acts as a critical fail-safe against premature loss of hematopoietic stem cells and development of T-ALL

Common molecular machineries between hematopoietic stem cell (HSC) maintenance and leukemia prevention have been highlighted. The tumor suppressor Fbxw7 (F-box and WD-40 domain protein 7), a subunit of an SCF-type ubiquitin ligase complex, induces the degradation of positive regulators of the cell cycle. We demonstrate that inactivation of Fbxw7 in hematopoietic cells causes premature depletion of HSCs due to active cell cycling and p53-dependent apoptosis. Interestingly, Fbxw7 deletion also confers a selective advantage to cells with suppressed p53 function, eventually leading to development of T-cell acute lymphoblastic leukemia (T-ALL). Thus, Fbxw7 functions as a fail-safe mechanism against both premature HSC loss and leukemogenesis.     

Renal oncocytoma developed in a long-term hemodialysis patient

A case of renal oncocytoma which developed in a 38-year-old Japanese woman after 7 years of maintenance hemodialysis is reported. An encapsulated round tumor with a diameter of about 5 cm was incidentally discovered by abdominal echography. This is the first case of renal oncocytoma found in a long-term hemodialysis patient. Identification and differentiation of this subgroup from renal carcinomas are very important because of its benign nature. Careful clinicopathological investigation of renal tumors should therefore be required in hemodialysis patients.