Thoracic wall reconstruction for primary malignancies in children: short- and long-term results.

AIM: Primary thoracic wall malignancy is a rare and diverse entity in children. Surgical treatment commonly involves major chest wall resection causing large defects requiring complex reconstruction. In adults, the use of alloplastic and/or xenogenic materials and muscle flap repair is well established. However, literature provides only little information on procedures in children. We report our experience in 8 consecutive children who underwent chest wall resection and reconstruction with regard to surgical treatment and outcome. PATIENTS AND METHODS: Retrospective study of all children with primary malignant chest wall tumors requiring rib resection and reconstruction with prosthetic material performed in our institution between November 2002 and April 2010. Endpoints were postoperative complications and long-term results, focusing on scoliosis defined radiologically by the Cobb angle. RESULTS: 8 children (7 male, 1 female) with a median age of 10.6 (4.1-18.9) years underwent resection of thoracic wall tumors. A mean number of 3 (1-5) ribs were resected. Stability was obtained using rigid prosthetic material (STRATOS™ titanium bar) in 2 patients and/or non-rigid prosthetic material (Goretex® patch in 6 patients, Vicryl® patch in 3 patients, Tutopatch® in 1 patient). A muscular flap was added in 5 patients. Postoperative complications included superficial wound infection (n = 2) and dislocation of a titanium bar necessitating removal in 1 patient. No infections of the prosthetic material were observed. No perioperative mortality occurred. At a mean follow-up of 37.5 (4-97) months, 6 patients were alive. 2 patients died due to early tumor recurrence. Mild scoliosis (Cobb angle 10-20°) was detected in 2 of the surviving patients (33%). CONCLUSION: Surgical reconstruction after resection of malignant thoracic wall tumors using non-rigid prosthetic material is safe and effective in pediatric patients, whereas rigid prosthetic material might dislocate. Scoliosis represents a long-term complication after chest wall reconstruction and should be monitored during routine follow-up.

Intravenous and oral sequential itraconazole antifungal prophylaxis in paediatric stem cell transplantation recipients: a pilot study for evaluation of safety and efficacy.

This single-centre, retrospective, observational pilot study was performed to evaluate the safety and efficacy of intravenous and oral itraconazole prophylaxis in paediatric haematopoietic stem cell transplantation (HCT). Study end-points were proven invasive fungal infection (IFI), survival, adverse reactions and graft-vs.-host disease (GVHD); 53 children and one young adult (median age 8.6 yr; range 0.4-18.3) transplanted between November 2001 and August 2004 were included in this study. Itraconazole was given intravenously from day +3 after HCT until oral medication became possible and continued until day +100 after HCT. Two proven new IFI in the itraconazole group (candidiasis, n = 1; aspergillosis, n = 1) were observed. After a median follow-up of 1.6 yr (0.3-6.1), six deaths (8%) were seen; 24 patients (45%) developed GVHD degree I-II, three children (6%) had GVHD degree III-IV. In 11 of 53 patients (21%), itraconazole prophylaxis was discontinued prematurely, mostly because of fever of unknown origin (n = 7). In total, 21 of 53 (40%) of the children had abnormal results of laboratory investigations during the prophylaxis. The results of this pilot study indicate that itraconazole prophylaxis during HCT in children is feasible and safe, despite abnormal laboratory results. The efficacy in terms of prevention of IFI, however, has to be addressed in a prospective large-scale study.

Multiplex PCR for simultaneous detection of the most frequent T cell receptor-delta gene rearrangements in childhood ALL.

A rapid and simple multiplex polymerase chain reaction (PCR) is described that is capable of identifying the six most frequent rearrangements of the T cell receptor (TCR)-delta gene segments in childhood acute lymphoblastic leukemia (ALL). The PCR products amplified in a single reaction are of different size for each TCR-delta gene rearrangement. Therefore, they are readily and unambiguously distinguished after agarose gel electrophoresis and assigned to a specific V-D-J gene rearrangement. There is no need for labor-intensive and time-consuming Southern blot hybridization or nested PCR. To evaluate the multiplex assay we chose 45 DNA samples of childhood ALL analyzed beforehand for TCR-delta gene rearrangements by Southern blot and single PCR of which 30 showed TCR-delta gene rearrangements. The multiplex PCR results corresponded to the Southern blot and single PCR analyses. The described multiplex PCR enables the detection of clonal markers in about 50% of patients in order to monitor minimal residual disease (MRD) in prospective studies with a high turnover of samples.

Clinical features and outcome of children with first marrow relapse of acute lymphoblastic leukemia expressing BCR-ABL fusion transcripts. BFM Relapse Study Group.

Although the Philadelphia chromosome (Ph1) has been identified as an adverse prognostic factor in acute lymphoblastic leukemia (ALL), little is known about the incidence and clinical course of relapsed Ph1-positive ALL in children. The incidence was determined by screening of 170 consecutive children with first bone marrow relapse of ALL using the reverse transcriptase-polymerase chain reaction (RT-PCR) and comparison, with cytogenetic analysis. Among these 170 children, 20 (12%) were found to be BCR-ABL-positive, representing a rate that is about three times higher than that reported for newly diagnosed ALL. Ten of the cases were identified by RT-PCR only. In none of the 21 patients with T-cell immunophenotypes could an expression of the BCR-ABL mRNA be detected. BCR-ABL positivity was associated with a significantly shorter duration of first remission (P = .0086) and higher white blood cell (P = .0157) and blast cell counts (P = .0304) at relapse diagnosis. All patients were treated according to the ALL-REZ BFM 87 and 90 relapse trials of the BFM Relapse Study Group. The intensive multiagent chemotherapy induced a second complete remission in only 60% of children with BCR-ABL-positive ALL compared with in 91% of those without BCR-ABL expression (P = .0023). The prognosis of BCR-ABL-positive ALL in children is poor, with a probability of event-free survival at 2 years of 8% versus 50% in those without BCR-ABL mRNA or cytogenetic analysis should become part of the routine diagnostic panel for children with newly diagnosed ALL and is fundamental for children presenting with an early bone marrow relapse.

Low-dose natural interleukin-2 and recombinant interferon-gamma following autologous bone marrow grafts in pediatric patients with high-risk acute leukemia.

Twenty-two patients with high risk hematologic malignancies (13 c-ALL, two B-ALL/NHL, four T-ALL, two AML M2, one pre-pre B-ALL) entered a phase I/II trial with cyclic administration of low dose natural interleukin-2/recombinant interferon-gamma (nIL-2/rIFN-gamma) following autologous bone marrow transplantation (ABMT), in order to induce a cytotoxic antileukemic effect. Eighteen patients subsequently relapsed, corresponding to a Kaplan-Meier estimate of disease-free survival (DFS) of 18%. Compared with a historical group of autologous bone marrow recipients who have not received immunotherapy, there is no significant difference according to DFS. Immunophenotyping of peripheral lymphocytes at the onset and end of therapy cycles revealed the most significant mean increase among the NK cell population (262/microliters +/- 51 vs. 354/microliters +/- 36, p = 0.004). However, even CD3 positive T cells rose significantly (591/microliters vs. 689/microliters, p = 0.04). In vitro NK cell activity tested against the NK sensitive myeloid leukemic cell line K562, and LAK cell activity tested against the LAK sensitive Burkitt lymphoma cell line Raji, was only low. An additional in vitro stimulus with nIL2, however, led to a therapy-dependent increase of cytotoxicity which was significant against Raji cells (25% +/- 4 vs. 41% +/- 5, p = 0.0124) indicating that low dose nIL2/rIFN-gamma enhances precursors of potentially cytotoxic cells in vivo.

[Renal cell cancer in childhood]. / Nierenzellkarzinom im Kindesalter.

Renal cell carcinoma is a rare disease in children and difficult to distinguish from Wilms-tumor before surgery. We present case histories of two children with renal cell carcinoma and discuss the problems of differential diagnosis versus nephroblastoma, therapy and prognosis. In contrast to Wilms-tumors, the most common kidney-tumor in children occurring mostly in young infants, renal cell carcinoma is rare in childhood and predominantly manifests in school-age. Only a few cases of renal cell carcinoma in younger children are described in the literature. Diagnostic imaging cannot reliably distinguish renal cell carcinoma from other neoplasm of the kidney. However, hematuria in patients with small tumors or no response to preoperative chemotherapy may indicate the presence of renal cell carcinoma rather than nephroblastoma. The determination of "tumor-associated trypsin inhibitor" (TATI) might give further contribution of differential diagnosis. It was measured only in one of our patients and was markedly elevated. Complete surgical resection (nephrectomy with lymphadenectomy) is a curative therapy in patients with tumors limited to the kidney. Chemotherapy and irradiation show no convincing effect. In metastatic tumors therapy with interleukin 2 may be successful.

Oxygen transport in congenital heart disease: influence of fetal hemoglobin, red cell pH, and 2,3-diphosphoglycerate.

In 48 individuals (age 1 day to 13 years) with congenital heart disease, blood oxygen transport function was studied in order to evaluate adaptive changes in shunt hypoxemia and to investigate the in vivo regulation of erythrocyte 2, 3-diphosphoglycerate concentration (RBC 2, 3-DPG) in the presence of fetal hemoglobin (HbF). Arterial pO2 and oxygen content, oxygen capacity, acid base status, oxygen affinity, HbF fraction, plasma pH, red cell pH, and RBC 2, 3-DPG were determined. During the first 50 days of life values of standard P50 (stdP50) (37, pH 7.4), actual in vivo P50 (actP50), RBC 2, 3-DPG, O2 capacity, arterial plasma pH, and red cell pH were scattered around the normal range, although tending to low values for stdP50 and arterial plasma pH and to high values for O2 capacity. After the third month, stdP50 actP50, RBC 2, 3-DPG, O2 capacity, and red cell pH were found to be elevated. Plasma pH and actP50 were scattered around the normal range (Figs. 1 and 2). Intraerythrocytic pH in hypoxemic infants was increased compared with normal children when related to plasma pH (Fig. 3). A close to normal intraerythrocytic pH was therefore found in the hypoxemic infants with low plasma pH, and an increased intraerythrocytic pH in the hypoxemic children with normal plasma pH (Fig. 1). A significant negative correlation exists between erythrocyte H+ ion and 2, 3-DPG concentration (Fig. 5); regression constants derived from data at high (mean 47%) and low (mean 9%) fractions of HbF are not significantly different (Regression Equations 8 and 11 in Table 1). Thus, the known difference in 2, 3-DPG binding to fetal or adult deoxyhemoglobin does not measurably influence the erythrocyte 2, 3-DPG concentration, indicating that in vivo the 2, 3-DPG synthesis in hypoxia is virtually regulated by the erythrocyte pH, which in turn is determined by plasma pH and the oxygenation state of hemoglobin.