[An original reconstruction technique for double upper white lip defect]. / Une technique originale de réparation d'une double perte de substance de l'hémilèvre supérieure blanche.

INTRODUCTION: Herein we report a case of a surgical repair of double substance loss along the nasolabial groove by means of a double superior advancement flap from the cheek to the upper lip that we have here called the "double jigsaw puzzle" flap. OBSERVATION: A 58-year-old man underwent surgery for 2 basal cell carcinomas located in the right white upper lip. The two lesions were first removed and the two defects were then carried over to the cheek symmetrically along the nasolabial groove. Two triangular "lugs" were excised on both sides to allow horizontal advancement of the cheek to the upper lip to fill the 2 gaps from the upper lip excisions like 2 pieces of a puzzle. The nasolabial groove was then recreated by deep anchoring stitches, with suturing comprising superficial stitches. DISCUSSION: This surgical flap can be created quickly and easily and yields good aesthetic results in the immediate postoperative period and in the longer term, and the scar is totally masked within the nasolabial fold. The only limitation to a good aesthetic outcome is the presence of a small area of hairless skin within what constitutes an area of hair growth in male subjects.

A pilot study of neuropsychological functions, APOE and amyloid imaging in patients with gliomas.

Brain tumor patients treated with radiotherapy (RT) often develop cognitive dysfunction, and recent studies suggest that the APOE ε-4 allele may influence cognitive outcome. The ε-4 allele is known to promote beta (ß) amyloid deposition in the cortex, and preliminary evidence suggests that RT may be associated with this process. However, it is unknown whether ß-amyloid accumulation contributes to treatment neurotoxicity. In this pilot study, we assessed neuropsychological functions and ß-amyloid retention using 18F-florbetaben (FBB) PET in a subset of brain tumor patients who participated in our study of APOE polymorphisms and cognitive functions. Twenty glioma patients treated with conformal RT ± chemotherapy participated in the study: 6 were APOE ε-4 carriers and 14 were non-ε-4 carriers. Patients completed a neuropsychological re-evaluation (mean time interval = 5 years, SD = 0.83) and brain MRI and FBB PET scans. Wilcoxon signed-rank test comparisons between prior and current neuropsychological assessments showed a significant decline in attention (Brief Test of Attention, p = 0.018), and a near significant decline in verbal learning (Hopkins Verbal learning Test-Learning, p = 0.07). Comparisons by APOE status showed significant differences over time in attention/working memory (WAIS-III digits forward, p = 0.028 and digits backward, p = 0.032), with a decline among APOE ε-4 carriers. There were no significant differences in any of the FBB PET analyses between APOE ε-4 carriers and non-ε-4 carriers. The findings suggest that glioma patients may experience worsening in attention and executive functions several years after treatment, and that the APOE ε-4 allele may modulate cognitive decline, but independent of increased ß-amyloid deposition.

Prognostic awareness and communication preferences among caregivers of patients with malignant glioma.

OBJECTIVE: Malignant glioma (MG) is a devastating neuro-oncologic disease with almost invariably poor prognosis, yet many families facing malignant glioma have poor prognostic awareness (PA), or the awareness of the patient's incurable disease and shortened life expectancy. Accurate PA is associated with favorable medical outcomes at end-of-life for patients and psychosocial outcomes for informal caregivers (ICs) through bereavement. To date, however, no study has specifically examined PA among MG ICs and the information they receive that shapes their awareness. METHODS: Thirty-two ICs of patients with malignant glioma completed a semi-structured assessment of their awareness of the incurability and life expectancy of their loved one's illness, and to understand their sources of prognostic information and preferences for communication of prognostic information. RESULTS: Twenty-two (69%) ICs had full PA-awareness of the incurability of malignant glioma and accurate estimates of their loved ones' life expectancy. Twenty-three (72%) felt that prognostic information was extremely or very important to possess, and 16 (50%) desired more prognostic information. The majority of ICs received prognostic information from physicians and the Internet. Qualitative analyses revealed that many ICs had difficulty navigating medical encounters in which they concurrently wanted to elicit prognostic information from physicians and protect patients from such information. CONCLUSIONS: Accurate and timely PA is necessary for ICs to serve as critical members of health care teams. Interventions are needed to foster ICs' skills in navigating prognostic communication with patients and health care providers and thereby improve their ability to advocate for their loved one's wishes.

Head and neck presentations of B-NHL and B-AL in children/adolescents: experience of the LMB89 study.

PURPOSE: Describe the epidemiology, clinical profiles and outcomes associated with head and neck (H&N) involvement in children/adolescents with B-cell non-Hodgkin lymphoma (B-NHL). METHODS: Analysis of children/adolescents with H&N B-NHL prospectively enrolled in the SFOP LMB-89 trial (July 1989-June 1996). RESULTS: One hundred and twelve of 561 patients (20%) had H&N involvement. The mean age of the patients was 8.4 years. Murphy staging differed between the H&N patients and the others (P < 0.0001): 9% versus 5% of the patients presented with stage I disease, 36% versus 11% presented with stage II disease, 12% versus 59% presented with stage III disease, 17% versus 10% with stage IV disease and 27% versus 16% with B-AL. Twenty-nine H&N patients (26%) had CNS involvement at diagnosis versus 8.5% in the group without H&N involvement (P < 0.0001). Patients were treated according to the LMB89 protocol: 3 H&N patients were allocated to group A, 70 to group B and 39 to group C. Ninety-seven percent of H&N patients achieved CR and event-free and overall survival at 4 years was 95.5% (5 deaths in patients with CNS disease). On multivariate analysis, EFS was significantly better in H&N patients than in non-H&N patients (P = 0.021), but not OS (P = 0.11). CONCLUSION: The H&N site is the second most common location for B-NHL at diagnosis and is more frequently associated with disseminated disease and CNS involvement than other sites. However, outcomes are no worse for these patients than for the rest of the population.

Deregulation of the platelet-derived growth factor B-chain gene via fusion with collagen gene COL1A1 in dermatofibrosarcoma protuberans and giant-cell fibroblastoma.

Dermatofibrosarcoma protuberans (DP), an infiltrative skin tumour of intermediate malignancy, presents specific features such as reciprocal translocations t(17;22)(q22;q13) and supernumerary ring chromosomes derived from the t(17;22). In this report, the breakpoints from translocations and rings in DP and its juvenile form, giant cell fibroblastoma (GCF), were characterised on the genomic and RNA level. These rearrangements fuse the platelet-derived growth factor B-chain (PDGFB, c-sis proto-oncogene) and the collagen type I alpha 1 (COL1A1) genes. PDGFB has transforming activity and is a potent mitogen for a number of cell types, but its role in oncogenic processes is not fully understood. COL1A1 is a major constituent of the connective tissue matrix. Neither PDGFB nor COL1A1 have so far been implicated in any tumour translocations. These gene fusions delete exon 1 of PDGFB, and release this growth factor from its normal regulation.

Reduction of fibrogenesis by selective delivery of a Rho kinase inhibitor to hepatic stellate cells in mice.

One of the pathways activated during liver fibrosis is the Rho kinase pathway, which regulates activation, migration, and contraction of hepatic stellate cells (HSC). Inhibition of this kinase by the Rho kinase inhibitor Y27632 [(+)-(R)-trans- 4-(1-aminoethyl)-N-(4-pyridyl)cyclohexanecarboxamide dihydrochloride] has been shown to reduce fibrosis in animal models. However, kinase expression is ubiquitous, so any inhibitor may affect many cell types. We hypothesize that cell-specific delivery of a kinase inhibitor will be beneficial. Therefore, we conjugated Y27632 to the carrier mannose-6-phosphate (M6P) human serum albumin (HSA), which is taken up specifically in activated HSC through the M6P/insulin-like growth factor II receptor. This conjugate decreased protein expression of phosphorylated myosin light chain 2 (pMLC2) and vinculin, downstream of Rho kinase, in activated primary HSC and decreased the migration and contraction of HSC. In an ex vivo model, free Y27632 decreased contractility of rat aortas, whereas the Y27-conjugate did not, showing that the Y27-conjugate does not affect nontarget tissue. In chronic CCl(4)-induced liver fibrosis, both free drug and conjugate reduced HSC activation; however, only the Y27-conjugate significantly reduced collagen deposition. Treatment with the Y27-conjugate, but not with free drug, reduced pMLC2 expression in livers 24 h after injection, demonstrating prolonged inhibition of the Rho kinase pathway. The Rho kinase inhibitor Y27632 can be specifically targeted to HSC using M6PHSA, decreasing its effects in nontarget tissues. The targeted drug effectively reduced fibrotic parameters in vivo via the inhibition of the Rho kinase pathway.

Surgical treatment of renovascular hypertension in children.

OBJECTIVES: The aim of this retrospective study was to report the author's experience of the surgical treatment of renovascular hypertension in children and to define the role of surgery in its treatment. MATERIAL AND METHODS: This series includes 85 patients (50 girls, 35 boys), 28 months to 18 years of age (mean: 10.3) operated on from 1970 to 2005. All patients had arterial hypertension and underwent the investigations usually performed in hypertensive patients. Renal artery lesions were bilateral in 26 cases. Due to bilateral procedures and to secondary or late reoperations, the number of surgical procedures was 114 (15 nephrectomies and 99 arterial repairs). RESULTS: Fibrodysplasia of the renal artery was the prevailing pathologic factor (71%). Associated vascular lesions were observed in 61% of the patients. There was no postoperative death in this series. Seven postoperative thromboses occurred (7% of the repairs). The complete cure of arterial hypertension was obtained in 82% of the patients. In young children, growth of the repairs was normal when age increased. CONCLUSION: Surgery still holds a prominent place in the treatment of renovascular hypertension in children. Its prognosis is favourable since atheroma or organ lesions are usually lacking.

Renal targeting of kinase inhibitors.

Activation of proximal tubular cells by fibrotic and inflammatory mediators is an important hallmark of chronic kidney disease. We have developed a novel strategy to intervene in renal fibrosis, by means of locally delivered kinase inhibitors. Such compounds will display enhanced activity within tubular cells and reduced unwanted systemic effects. In our approach kinase inhibitors are linked to the renal carrier lysozyme using a platinum-based linker that binds drugs via a coordinative linkage. Many kinase inhibitors contain aromatic nitrogen atoms able to bind to this linker without the need of prior derivatization. The resulting drug-lysozyme conjugates are rapidly filtered in the glomerulus into the tubular lumen and subsequently reabsorbed via the endocytic pathway for clearance of low-molecular weight proteins. An important property of the formed conjugates is their in vivo stability and the sustained drug release profile within target cells. This review summarizes the state-of-the-art of drug targeting to the kidney. Furthermore, we will highlight recent results obtained with kinase inhibitor-lysozyme conjugates targeted to different kinases, i.e. the transforming growth factor (TGF)-beta-receptor kinase, p38 MAPkinase and Rho-associated kinase. Both in vitro and in vivo results demonstrated their efficient tubular uptake and beneficial therapeutic effects, superior to treatment with free kinase inhibitors. These proof-of-concept studies clearly indicate the feasibility of drug targeting for improving the renal specificity of kinase inhibitors.

Flaujeac trait. Deficiency of human plasma kininogen.

Flaujeac trait plasma resembled Hageman trait or Fletcher trait, in that the intrinsic coagulation pathway, plasma fibinolytic pathway, kinin-forming system, permeability factor of dilution (PF/dil) phenomenon were abnormal. The defect in each assay was reconstituted by afactor separable from Hageman factor or Fletcher factor. This substance was an alpha-globulin with an approximate mol wt of 170,000. Flaujeac plasma did not release a kinin upon incubation with kallikrein and was deficient in total kininogen antigen. Antiserum to kininogen inhibited the activity of the factor in solution. Flaufeac factor was identified as a kininogen of high molecular weight (HMW-kininogen). The mean total kininogen antigen in four children of the proposita was 51% (range 34-62%) of normal. A functional coagulation assay of HMW-kininogen in the children was 34% (range 23-55%). The results were consistent with autosomal recessive inheritance. The plasma pathways of intrinsic coagulation, fibrinolysis, kinin formation, and PF/dil generation are dependent upon HMW-kininogen. We believe this is the first demonstration of biological function for a kininogen apart from its role as a substrate for kallikreins.

Flaujeac factor deficiency. Reconstitution with highly purified bovine high molecular weight-kininogen and delineation of a new permeability-enhancing peptide released by plasma kallikrein from bovine high molecular weight-kininogen.

Flaujeac trait is the functional deficiency of a plasma protein of the intrinsic coagulation, kinin-forming, and plasma fibrinolytic pathways. The Flaujeac factor in man has been isolated and tentatively identified as a kininogen of high molecular weight (HMW). Highly purified bovine HMW-kininogen, but not bovine low molecular weight kininogen, repaired Flaujeac factor deficiency. The two subspecies of this molecule, HMW-kininogen a and HMW-kininogen b, also corrected Flaujeac factor deficiency. When bovine HMW-kininogen was incubated with bovine plasma kallikrein, kinin-free HMW-kininogen, bradykinin, and a glycopeptide fragment (peptide 1-2; 12,584 daltons) were rapidly released. None of these fragmentation products corrected Flaujeac factor deficiency alone or in mixtures. The function of HMW-kininogen appeared to depend upon the structural integrity of the native molecule. When injected in concentrations of 2 pmol-8 nmol/0.1 ml, peptide 1-2 caused increased vascular permeability in rabbits, rats, or guinea pigs. The enhanced permeability was maximal within 1-2 min and terminated in 5-10 min, differing from that of bradykinin or histamine. Injected together in equimolar amounts, peptide 1-2 and bradykinin produced a synergistic permeability response which was immediate in onset as well as prolonged in duration. Peptide 1-2 is a rapidly acting, highly basic glyco-peptide which mediates increased vascular permeability in a complementary and synergistic manner with bradykinin.

Brain structure and function in patients with ovarian cancer treated with first-line chemotherapy: a pilot study.

Women with ovarian cancer often undergo chemotherapy involving multiple agents. However, little is known about treatment-related central neurotoxicity in this population. The goal of this cross-sectional study was to assess brain structure and function and neurocognitive abilities in patients with ovarian cancer following first-line chemotherapy. Eighteen patients with ovarian, peritoneal and fallopian tube cancer and eighteen healthy controls matched for gender, age and education participated in the study. The patients were evaluated 1-4 months following completion of first-line taxane/platinum chemotherapy. All participants underwent structural and functional magnetic resonance imaging (MRI), and completed neuropsychological tests of attention, memory and executive functions. Neuroimaging assessments included voxel-based morphometry (VBM) for measuring gray matter (GM) volume, and functional MRI (fMRI) during the N-back working memory task. The results of VBM showed that patients had significantly reduced GM volume compared to healthy controls in the right middle/superior frontal gyrus, and in the left supramarginal gyrus and left inferior parietal lobule. fMRI results indicated significantly decreased activation in patients relative to healthy controls in the left middle frontal gyrus and left inferior parietal lobule during the N-back task (1/2/3-back >0-back). There were no statistically significant differences between the two groups on the neuropsychological tests. This is the first study showing structural and functional alterations involving frontal and parietal regions in patients with ovarian cancer treated with first-line chemotherapy. These findings are congruent with studies involving women with breast cancer, and provide additional supporting evidence for central neurotoxicity associated with taxane/platinum chemotherapy.

Soft tissue sarcoma or malignant mesenchymal tumors in the first year of life: experience of the International Society of Pediatric Oncology (SIOP) Malignant Mesenchymal Tumor Committee.

PURPOSE: To describe the outcome of infants with a histologically confirmed diagnosis of malignant mesenchymal tumor (MMT) included in the International Society of Paediatric Oncology studies MMT 84 and MMT 89. PATIENTS AND METHODS: One hundred two infants (< or = 12 months old) were included. Twenty-four children were less than 3 months old, and 16 were less than 1 month old. Sixty-four patients had rhabdomyosarcoma (RMS), 26 had undifferentiated sarcoma, and 12 had other histology. Clinical TNM stage was stage I (41%), II (39%), III (6%), and IV (14%). First-line treatment was ifosfamide, vincristine, dactinomycin, whereas the second-line combination consisted of either cisplatin and doxorubicin (in MMT 84) or vincristine, carboplatin, etoposide/teniposide (in MMT 89). Chemotherapy doses were adapted to age. Local therapy was conservative surgery as often as possible. RESULTS: After a median follow-up of 7.8 years (range, 0.1 to 13 years), 5-year overall survival (OS) and event-free survival rates were 66% and 55% for the total study population and 72% and 60% for nonmetastatic patients, respectively. Only two of 13 stage IV patients survived. Sixty-seven percent of newborn infants survived. Infants with alveolar subtype had a poorer survival than those with non-RMS MMT or nonalveolar RMS (5-year OS, 37% v 75% or 82%, respectively; P = .002). When compared with older children with MMT, young age does not seem to be an important prognostic factor. CONCLUSION: OS was satisfactory even when local treatment was not aggressive, although the prognosis was poor for infants with alveolar RMS or metastatic tumors. Chemotherapy toxicity was manageable with appropriate dose modification.

X-ray structure of human nucleoside diphosphate kinase B complexed with GDP at 2 A resolution.

BACKGROUND: Nucleoside diphosphate (NDP) kinases provide precursors for DNA and RNA synthesis. In mammals, these enzymes are also involved in cell regulations. Human NDP kinase B, product of the human nm23-H2 gene, is both an enzyme and a transcription factor. It activates transcription of the c-myc oncogene independently of its catalytic function, by binding to its promoter DNA. How do the two functions coexist? RESULTS: Recombinant human NDP kinase B was co-crystallized with GDP. The X-ray structure was solved at 2.0 A resolution by molecular replacement from the homologous Drosophila Awd protein. Both enzymes are homo-hexamers with a characteristic beta alpha beta beta alpha beta fold. GDP binds near the active site His118. The guanine base is in a surface cleft and interacts with the C terminus of another subunit. CONCLUSIONS: The beta alpha beta beta alpha beta fold, also present in the 'palm' domain of Escherichia coli DNA polymerase I and HIV reverse transcriptase, is both a mononucleotide- and a polynucleotide-binding fold. If NDP kinase B binds DNA in the same way as the polymerases, the enzyme must undergo a conformation change in order to carry out gene activation.

Dictyostelium nucleoside diphosphate kinase highly homologous to Nm23 and Awd proteins involved in mammalian tumor metastasis and Drosophila development.

Two complementary DNAs (cDNAs) previously isolated, one by functional screening and the other by immunological screening of a Dictyostelium discoideum expression library, encode two proteins, Gip17 and Guk7.2, sharing 71% homology. In the present study, we found that the expression of their messenger RNAs (mRNAs) is developmentally regulated, with a sharp decrease during the first hours of differentiation. The Gip17 protein was purified to homogeneity from D. discoideum amoebas and from recombinant Escherichia coli and was conclusively identified as a nucleoside diphosphate (NDP) kinase. NDP kinases play a major role in synthesis of nucleoside triphosphates and, in many systems, are found associated with guanosine triphosphate (GTP)-binding proteins. We found the Gip17 protein to be 77% homologous to the human Nm23 protein and 75% homologous to the Drosophila melanogaster Awd protein. The levels of murine and human nm23 mRNA and Nm23 protein are significantly reduced in tumor cells of high metastatic potential, suggesting that Nm23 is involved in suppression of mammalian tumor metastasis, and mutants of the awd gene exhibit widespread development abnormalities, suggesting that Awd is involved in D. melanogaster development. The high percentage of homology of the Gip17 and Guk7.2 proteins with the Nm23 and Awd proteins indicates that Nm23 and Awd also have nucleoside diphosphate kinase activity. Possible modulations in the activity of this metabolic enzyme could be related to the altered metabolism of tumor cells and the control of metastatic potential. Our results point to an unexpected role of NDP kinase in development, growth control, and oncogenic transformation.

[Vascular complications of lumbar disk surgery]. / Les complications vasculaires de la chirurgie discale lombaire.

Vascular complications of lumbar disc surgery are rare (about 0,04% of discectomies) but very severe. Great variations of the anatomical lesions and of their clinical aspects may be observed. These lesions are often unrecognised during the operation and they are sometimes identified several years after the injury. The treatment is mainly surgical but percutaneous endovascular treatment has been recently performed successfully in several patients.

[Panniculectomy as first part of colorectal resection for cancer in a morbidly obese patient]. / La panniculectomie première comme voie d'abord dans la résection colorectale pour cancer chez le grand obèse.

We reported the case of a patient presenting a rectal cancer of the upper part with a BMI at 59 which was previously considered as a contraindication to surgery. To perform the operation we had to make as first step of the procedure a panniculectomy. The technique made possible the rectal resection under good conditions, without blood transfusion. The post-operative course was uneventful except a pulmonary embolism controlled with medical treatment. This procedure is feasible in colorectal surgery.

In vivo local expansion of clonal T cell subpopulations in renal cell carcinoma.

Renal cell carcinoma (RCC) is one human tumor to which the immune response may control the growth of tumor cells. These tumors are infiltrated by a large mononuclear infiltrate mainly composed of T lymphocytes. To characterize the lymphocytes infiltrating RCC, we analyzed the molecular structure of the T cell receptor (TCR) alpha and beta chains in tumor and paired peripheral blood lymphocytes from a series of 6 untreated patients. We first determined V alpha and V beta gene segment usage by PCR using a panel of V specific oligonucleotide primers (V alpha 1-w29 and V beta 1-w24). A highly diverse usage of TCR V alpha and V beta gene usage was observed in 5 of 6 tumors. In addition, the few tumor overexpressed V beta specificities detected by reverse transcription-PCR were shown to contain minor T cell expansions. Strikingly, 1 of the 6 tumor studied displayed a skewed TCR repertoire with V beta 4 transcript representing 25% of the TCR signals. Clonality of the tumor overexpressed V beta transcripts was analyzed by CDR3 size distribution analysis. In the particular tumor displaying a biased repertoire large expansions of T cell subpopulations were detected (particularly in V beta 4) specifically at the tumor site. Such T cells may be expanded locally in response to tumor antigens.

Tumor-specific up-regulation of the nonclassical class I HLA-G antigen expression in renal carcinoma.

HLA-G is a nonclassical class I antigen mainly expressed at the maternofetal interface during pregnancy where it is thought to down-modulate maternal immune response against the semiallogeneic fetus. Recent studies indicate that ectopic up-regulation of HLA-G expression on melanoma cells may also favor their escape from antitumor immune response. HLA-G expression was here investigated on paraffin-embedded tumor and adjacent normal renal tissues of 18 renal cell carcinoma (RCC) patients. We provide evidence that HLA-G antigen is differentially expressed in carcinoma and normal renal cells and that up-regulation of this antigen in the tumor cells is more frequent than alterations of other MHC class I or class II antigens. We also demonstrated that HLA-G cell surface expression and secretion is maintained in a tumor cell line (DM) established from an HLA-G-positive RCC lesion. Furthermore, we show that type I (alpha and beta) and, in particular, type II (gamma) IFN treatment enhances steady-state mRNA levels and cell surface expression of HLA-G in the DM cell line. As several studies suggest that HLA-G displays various functional features that allow down-modulation of immune response in vitro, we propose that selective in vivo expression of HLA-G may participate in the impairment of antitumor immunity in RCC.

Combined analysis of DNA ploidy index and N-myc genomic content in neuroblastoma.

The aim of the study was to assess, in a group of nonselected patients with neuroblastoma, the prognostic value of both N-myc gene amplification and DNA ploidy index, taking into account potential confounding factors such as age and stage. Of 59 patients studied, 23 were younger than 1 year at diagnosis, 31 presented with stage IV, 10 with stage III, 5 with stage II, 8 with stage I, and 4 with stage IV-S. N-myc genomic content was analyzed by Southern blot hybridization technique and N-myc amplification (greater than or equal to 3 copies/haploid genome) was present in 6 stage IV, 2 stage III, and 1 stage IV-S. The DNA ploidy index was analyzed by flow cytometry. Of the 59 neuroblastomas, 26 were diploid (DNA index, 1) and 33 were aneuploid (DNA index, greater than 1). The majority of the aneuploid tumors (28 of 33) were near-triploid with DNA indexes between 1.25 and 1.68, 4 were near-diploid (DNA index up to 1.18), and 1 was hypotetraploid (DNA index, 1.85). The proportion of near-triploid tumors was significantly greater among patients under 1 year of age and among patients presenting with stages I, II, and IV-S. Interestingly, 0 of 28 near-triploid neuroblastomas exhibited N-myc gene amplification, compared to 9 of 31 in the group of diploid, near-diploid, and hypotetraploid tumors (Fisher's exact test, P less than 0.001). Four factors were significantly related to a high risk of relapse in univariate analysis, i.e., age, stage, DNA index, and N-myc amplification. In multivariate analysis, only N-myc amplification and the DNA index remained significantly associated with a high risk of relapse. The 2-year disease-free survival rate was 94% (95% confidence interval, 77-98%) for patients with near-triploid neuroblastoma, compared to 45 and 11% (95% confidence interval, 32-70 and 4-23%) for patients with diploid or near-diploid tumors, without and with N-myc amplification, respectively. We concluded that the combination of N-myc and DNA index should be included in routine management of neuroblastoma.