Segmental chromosomal alterations have prognostic impact in neuroblastoma: a report from the INRG project.

BACKGROUND: In the INRG dataset, the hypothesis that any segmental chromosomal alteration might be of prognostic impact in neuroblastoma without MYCN amplification (MNA) was tested. METHODS: The presence of any segmental chromosomal alteration (chromosome 1p deletion, 11q deletion and/or chromosome 17q gain) defined a segmental genomic profile. Only tumours with a confirmed unaltered status for all three chromosome arms were considered as having no segmental chromosomal alterations. RESULTS: Among the 8800 patients in the INRG database, a genomic type could be attributed for 505 patients without MNA: 397 cases had a segmental genomic type, whereas 108 cases had an absence of any segmental alteration. A segmental genomic type was more frequent in patients >18 months and in stage 4 disease (P<0.0001). In univariate analysis, 11q deletion, 17q gain and a segmental genomic type were associated with a poorer event-free survival (EFS) (P<0.0001, P=0.0002 and P<0.0001, respectively). In multivariate analysis modelling EFS, the parameters age, stage and a segmental genomic type were retained in the model, whereas the individual genetic markers were not (P<0.0001 and RR=2.56; P=0.0002 and RR=1.8; P=0.01 and RR=1.7, respectively). CONCLUSION: A segmental genomic profile, rather than the single genetic markers, adds prognostic information to the clinical markers age and stage in neuroblastoma patients without MNA, underlining the importance of pangenomic studies.

Translevator anal anomalies with cutaneous fistulae passing deep to the scrotum.

METHODS: The authors present a series of 9 patients collected from 4 centers with translevator anal anomalies, each of which has a fistula tracking forward deep to the scrotum and opening at the peno-scrotal junction. Whereas some would appear to be covered ani in type, others are deeper and would appear to fit in with an intermediate type of classification emphasizing the idea of a "spectrum" of malformation. RESULTS: The anatomic arrangement, associated anomalies (eg, 2 had hypospadias), and surgical management is described briefly in each case. Careful examination may be necessary to identify the fistula. CONCLUSIONS: It is recommended that the surgery be individualized depending on the findings. On a theoretical embryologic basis there is abnormality in the formation of the outer genital folds, and there also may be abnormality in some cases of the inner genital folds.

A homeobox gene, HLXB9, is the major locus for dominantly inherited sacral agenesis.

Partial absence of the sacrum is a rare congenital defect which also occurs as an autosomal dominant trait; association with anterior meningocoele, presacral teratoma and anorectal abnormalities constitutes the Currarino triad (MIM 176450). Malformation at the caudal end of the developing notochord at approximately Carnegie stage 7 (16 post-ovulatory days), which results in aberrant secondary neurulation, can explain the observed pattern of anomalies. We previously reported linkage to 7q36 markers in two dominantly inherited sacral agenesis families. We now present data refining the initial subchromosomal localization in several additional hereditary sacral agenesis (HSA) families. We excluded several candidate genes before identifying patient-specific mutations in a homeobox gene, HLXB9, which was previously reported to map to 1q41-q42.1 and to be expressed in lymphoid and pancreatic tissues.

[Better survival in neuroblastoma?]. / Bedred overlevelse ved neuroblastom?

This study compares the five year absolute survival rates among neuroblastoma patients treated at the National Hospital, Oslo, during two periods of time, 1985-90 and 1967-81. The treatment regimens differed, the main difference was more radical operations and more intensive chemotherapy during the period 1985-90 (n = 27) than in 1967-81 (n = 58). The intensified treatment was accomplished without operative mortality and without lethal complications associated with the cytostatic medication. For localized neuroblastoma the survival rate rose from 64% to 93%. The results obtained for disseminated neuroblastoma (Evans' stage IV) remained poor, however, with survival rates of 0% in 1967-81 and 17% in 1985-90.

Effect of iopentol on renal function and its use for calculation of glomerular filtration rate in children.

Nineteen children received 99mTc-DTPA for renography. The next day they received a simultaneous injection of the non-ionic contrast medium iopentol for urography and another injection of 99mTc-DTPA. The glomerular filtration rate (GFR) was estimated from the plasma elimination of 99mTc-DTPA as well as iopentol. Serum concentrations of creatinine and beta 2-microglobulin, and urine concentrations of creatinine, beta 2-microglobulin, alkaline phosphatase, N-acetyl-glucosaminidase, and albumin were determined. A significant reduction (12 +/- 3%) of GFR was observed after the injection of iopentol, without a subsequent rise in serum creatinine or beta 2-microglobulin. The urinary excretion of albumin and beta 2-microglobulin remained unchanged, while the excretion of alkaline phosphatase and N-acetyl-glucosaminidase was significantly increased after the urography, indicating some tubular effects of iopentol. Iopentol caused few and mild adverse events, the diagnostic yield was high, and the small changes in the renal tubular function parameters are presumed to be without clinical importance. The observed depressive effect on the GFR demands further investigations before iopentol can be recommended as a GFR-marker in children.

[Better results with early surgical intervention in biliary atresia. Icterus in infants older than 14 days should be investigated!]. / Tidlig kirurgisk behandling bedrer resultatene ved gallegangsatresi. Icterus hos spedbarn etter 14 dagers alder skal utredes!

The average survival of patients with biliary atresia that remains untreated is 12 months. Early portoenterostomy, and subsequent liver transplantation if necessary, have improved survival dramatically. The success rate after portoenterostomy is inversely related to age at primary operation, and the results after liver transplantation are best in children who receive the transplant after the age of one year. Thus, early portoenterostomy will buy time and bring the patient into a group with a better prognosis if liver transplantation is performed later. Among infants older than two weeks of age with neonatal jaundice, patients with conjugated hyperbilirubinemia must be identified and referred for investigation. In this case ultrasonography is most important for discovering biliary atresia.

Progress in the treatment of biliary atresia: a plea for surgical intervention within the first two months of life in infants with persistent cholestasis.

During the period 1984-1991, 21 infants with biliary atresia were treated with Kasai's portoenterostomy. The median survival in infants operated on before the age of 60 days (55 (range 5-82) months) was significantly longer than the survival of children operated on after the age of 60 days (15 (1.5-38) months). At present there are 10 survivors with a median age of 54 (17-96) months; 6 with portoenterostomy and 4 after liver transplantation. Eight patients died of progressive liver failure and 3 died of causes not related to biliary atresia. Apart from blood tests, ultrasonography was the most important investigation before laparotomy in infants with cholestatic jaundice. Scintigraphy and liver biopsy added no further decisive information. Because early diagnosis and surgical treatment is important, only the well documented presence of a normal gallbladder can warrant postponement of an operation.

The clearance of iohexol as a measure of the glomerular filtration rate in children with chronic renal failure.

The plasma clearances of technetium-99m-labelled DTPA ([99Tcm]-DTPA) and the non-ionic contrast medium iohexol were estimated in 11 children with chronic renal failure for determination of the glomerular filtration rate (GFR). Equal values were obtained with the two substances provided plasma sampling was simultaneous, but when plasma was sampled within 3.5 h after injection of iohexol and [99Tcm]-DTPA the GFR was overestimated by more than 50%. For clearance values below 20 ml min-1 1.73 m-2, valid GFR estimates were obtained both from two plasma samples taken 3 h and 24 h after the injection of iohexol and from a single plasma sample taken 24 h after the injection.

A single plasma sample method for estimation of the glomerular filtration rate in infants and children using iohexol, I: Establishment of a body weight-related formula for the distribution volume of iohexol.

This study was performed in order to develop a method for estimation of the glomerular filtration rate (GFR) from a single plasma sample based upon the plasma disappearance rate of the non-ionic contrast medium iohexol. The apparent distribution volume for iohexol was measured in 100 infants and children and used for establishment of a weight-related empirical formula for the distribution volume. Using the distribution volume obtained by this formula, a preliminary GFR was calculated from the iodine concentration measured in a plasma sample taken 3 h after injection of iohexol. When this estimate was corrected by another empirically established correction factor, a high degree of agreement was found between a GFR reference method and the 3-h single plasma sample method. In another group of 13 children the 3-h single plasma sample GFR was estimated twice with a 2-day interval, and the day-to-day variations were found to be similar to those obtained with other standard methods.

A single plasma sample method for estimation of the glomerular filtration rate in infants and children using iohexol, II: Establishment of the optimal plasma sampling time and a comparison with the 99Tcm-DTPA method.

The glomerular filtration rate (GFR) can be determined from the plasma disappearance rate of the non-ionic contrast medium iohexol. A preceding study established the empirical formulae enabling the development of a single plasma sample method for estimation of GFR in infants and children. In the present study the validity of these empirical formulae was confirmed in examinations in 143 patients. The results of the single plasma sample method were similar to those of a standard 99Tcm-DTPA method, and also with those of a two plasma sample iohexol method. Evaluation of the results obtained with plasma sampling 1 h, 2 h, 3 h and 4 h after the injection of the contrast medium showed that the optimal sampling time was about 3 h after the injection.

[Autologous bone marrow transplantation in children--experience with neuroblastoma]. / Autolog beinmargstransplantasjon hos barn--erfaringer ved neuroblastom.

Autologous bone marrow transplantation permits the use of greatly intensified cytoreductive therapy for cancer. Since 1983 seven children with disseminated neuroblastoma (stage IV) were treated by this method. Five were treated in first, and one in second complete remission; one child was in partial remission. Tumor cell purging of the marrow inoculum was performed in five cases. All children had engraftment and were discharged from hospital free of disease. Relapse was observed in three children within two years. Four children remain healthy at follow-up 5-77 months after autotransplantation. We describe and discuss indications, methods, side effects and results.

Glomerular filtration rate estimated by X-ray fluorescence technique in children: comparison between the plasma disappearance of 99Tcm-DTPA and iohexol after urography.

The total plasma disappearance of the non-ionic contrast medium iohexol was determined by X-ray fluorescence technique following intravenous urography in 10 children aged between 2 and 13 years. For comparison the plasma disappearance of 99Tcm-DTPA was estimated both 2 days before and simultaneously with the iohexol study. High correlations between the three sets of data were found and no change in the glomerular filtration rate was detected following injection of contrast medium. It was also found that reliable estimates of the glomerular filtration rate can be obtained from two plasma samples of 1 ml each, taken 3 h and 4 h after the injection of the contrast medium.

Influence of urography on renal function in children. A double blind study with metrizoate and iohexol.

Thirty-two children were given either metrizoate or iohexol for urography in a double blind study. Mild to moderate adverse reactions were observed in all patients receiving metrizoate (15/15) and in 4 receiving iohexol (4/17). Alkaline phosphatase in urine was significantly increased 4 hours after the injection of both media, but had returned to pre-injection levels 16 hours later. The excretion of beta 2-microglobulin and albumin was not altered. In 9 children in the metrizoate group and 11 in the iohexol group the glomerular filtration rate (GFR) was determined before urography by the single injection 99Tcm-DTPA-technique and 3 to 4 hours after urography by measuring the plasma disappearance of the contrast medium with the x-ray fluorescence technique. No reduction of GFR was observed.

Torsion of a wandering spleen in an infant. Report of a case and a brief review of the literature.

A case of torsion of the wandering spleen in an infant is presented. The value and limitations of various imaging modalities in making a correct preoperative diagnosis are discussed and a brief review of the literature is given.

Distribution of ouabain-binding sites along the dog nephron.

To quantify the relative amount of ouabain bound to different segments of the nephron after in vivo injection of the drug, an autoradiographic (ARG) study was carried out. After intrarenal injection of [3H]ouabain (120 nmol kg-1 body wt, 0.9-1.2 Ci mol-1) to intact kidneys of three anaesthetized dogs, 69-89% of renal Na,K-ATPase activity was inhibited. Sodium reabsorption decreased by 21-54%. Sections for ARG were obtained from tissue slices frozen in liquid Freon, freeze-dried and embedded in resin. Almost no loss of activity occurred during processing and background activity was negligible after 23-36 days' exposure. The density of [3H]ouabain grains per mu 2 of tubular walls was 3.8 times higher over medullary ascending limbs of Henle's loop (MAL) and distal cortical tubules (DT) as compared to proximal tubules (PT). In terms of tubular length, the grain density of MAL exceeded that of PT by merely 35% since the cross-sectional area of the MAL was only 25% of that of PT. In DT, grain density in terms of tubular length was lower than in PT by 10%. Based on previous estimate of the absolute ouabain-binding capacity in MAL of 60 fmol mm-1 tubule, the ouabain-binding capacity in PT and DT would equal 45 and 40 fmol mm-1, respectively. From composite microphotographs, the relative volume of PT was estimated to be 42% of the total renal volume. This means that 47% of the total renal ouabain-binding sites are localized to PT, whereas MAL and DT together contain 51%.