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N L Carlsen

Publications and source records attributed to N L Carlsen.

35 records · Page 2Linked to original sources
PubMed1986

Prognostic factors in neuroblastomas treated in Denmark from 1943 to 1980. A statistical estimate of prognosis based on 253 cases.

Multivariate analysis on an unselected patient population consisting of all 253 children treated for neuroblastoma in Denmark during 1943 to 1980 shows that stage, age, and treatment given are independent prognostic variables. Calendar year of diagnosis, sex of the patient, and site of primary tumor were not significant prognostic factors. Further analysis shows that multimodal treatment with surgery, irradiation, and chemotherapy, especially in patients older than 1 year of age with Stage II disease, has influenced the survival significantly. The fact that age at diagnosis and the administration of chemotherapy have independent prognostic significance can be explained by the theory that all neuroblastomas are virtually congenital; therefore, the difference in age at diagnosis largely reflects the difference in growth rates of the tumor. Thus, according to this theory, age may be a measure of the probability of micrometastases in addition to the clinical extent or stage of the disease, as it represents the duration of the disease. Additional chemotherapy may thus have eradicated these micrometastases in the older children, since the age influence on Stage II disease disappeared when multimodal treatment was given in this study. The implications for treatment policy are discussed in view of this theory.

Age Factors↗
PubMed1986

Epidemiological investigations on neuroblastomas in Denmark 1943-1980.

During the period 1943-1980 a significant increase in the incidence of neuroblastoma was seen in Denmark. The incidence increased from a level corresponding to that in Finland to a level corresponding to that in the USA, and the increase appears to be continuing. The increase relates to children aged under 5 years, and is most pronounced in infants under 1 year. The incidence in the first year of life has, however, not yet reached the level of the USA. The increase in incidence is most likely a result of improved diagnosis, changes in the social composition of the population, and an increase in environmental carcinogens of importance in the induction of neuroblastomas. The incidence is lower in children of self-employed parents, and higher in infants of mothers aged under 20 or over 34 years. Aside from lower socio-economic circumstances for mothers under 20 years, no specific risk factors were revealed in this study. The observations of a family in which the mother has ganglioneuroma and both daughters have developed neuroblastoma, of a child who suffered from both neuroblastoma and neurofibromatosis von Recklinghausen, and of a significantly higher frequency of infants with signs of multicentric tumours in the offspring of mothers aged under 20 and over 34 years of age, is consistent with the two-hit theory of Knudson et al. (1972).

Adolescent↗
PubMed1986

Prognostic value of different staging systems in neuroblastomas and completeness of tumour excision.

Two hundred and fifty three patients were retrospectively assigned to eight different staging systems proposed for neuroblastomas, and the prognostic value of each staging system was evaluated individually. The ability of each system to predict prognosis was compared with the others and the system proposed by Evans et al found to be the best predictor, even better than the recently proposed Tumour-Nodes-Metastases staging system. This is probably due to the fact that factors other than the resectability of the tumour play a major role in the survival of these children. Age was found to have independent prognostic significance whatever staging system was used.

Age Factors↗
PubMed1985

Neuroblastomas treated at the four major child oncologic clinics in Denmark 1943-1980: an evaluation of 180 cases.

One hundred and eighty cases of neuroblastomas from the four child oncology clinics are reviewed. The overall cure rate was 24%. During the 38-year period, there was a significant increase in survival from 0% during the period of 1943-1950 to 32% during the period of 1971-1980. This improved survival rate is most likely a result of adjuvant chemotherapy. Forty percent of the patients appear chronically ill, which reflects the fact that nearly 60% have metastases when they are first seen. In localized disease (stages I-II), the prognosis was favourable (cure rate 69%), while the prognosis for disseminated disease (stage III-IV) was poor (cure rate 5%). A favourable outcome was seen in patients under 1 year (survival rate 46%), and in patients with primary tumours located in the neck or mediastinum (survival rate 48%). When related to stage, however, the survival rates for the former tumours were not significantly better in patients below 1 year or in patients with cervical or thoracic tumours. As is the case in other studies, we found that survival is significantly poorer in males.

Abdominal Neoplasms↗
PubMed1985

Comparison of long-term, low-dose pivmecillinam and nitrofurantoin in the control of recurrent urinary tract infection in children. An open, randomized, cross-over study.

Thirty-five children with a history of vesicoureteric reflux or with recurrent urinary tract infections were randomly allocated to low-dose prophylactic treatment with pivmecillinam or nitrofurantoin. After 6-10 months they were crossed over to the alternate drug for another 6 months, but only 24 completed the study because of lack of compliance or intolerance to nitrofurantoin. There was no significant difference in the long-term prophylactic effect between the two drugs, the overall infection rate being 0.7/patient-year. Pivmecillinam was significantly better tolerated than nitrofurantoin (P = 0.01). Nitrofurantoin effected no major change in the faecal flora, and nearly all urinary infections occurring during long-term treatment were caused by Escherichia coli. In contrast, a marked reduction of E. coli and a marked increase in Gram-positive cocci were found in the faecal flora during treatment with pivmecillinam. Seventy per cent of infections were caused by Streptococcus faecalis and only 20% by E. coli during pivmecillinam treatment (P = 0.001).

Adolescent↗
PubMed1984

Premature cranial synostosis in X-linked hypophosphatemic rickets: possible precipitation by 1-alpha-OH-cholecalciferol intoxication.

A child suffering from X-linked hypophosphatemic rickets developed vitamin D intoxication under treatment with 1-alpha-OH-cholecalciferol (1(OH)D3) and phosphorus. Beside the usual findings in this condition he showed precocious synostosis of the skull with signs of raised intracranial pressure. In view of earlier reports of coincidence of craniostenosis and X-linked hypophosphatemic rickets, we conclude that the possibility exists that intoxication with 1(OH)D3 has been the precipitating factor. In addition we found hypersensitivity to 1(OH)D3 2 months after cessation of treatment, and normal levels of calcitriol (1,25(OH)2D3) at the same time.

Cranial Sutures↗
PubMed1981

Neuroblastoma. Evaluation of 60 cases.

60 cases of neuroblastoma from the departments of paediatrics and paediatric surgery, Rigshospitalet, are reviewed. The overall cure rate was 35%. In localized disease (stages I--II) the prognosis was favourable (cure rate 78%), while the prognosis for disseminated disease (stages III--IV) was poor (cure rate 10.8%). Neuroblastomas in stage IV-S had a favourable prognosis in spite of metastases to the liver, skin and bone marrow. The clinical stage at the time of diagnosis was the only independent prognostic factor in this study.

Age Factors↗
PubMed1980

[Neuroblastoma].

Explore the source record for details and available documents.

Diagnosis, Differential↗
PubMedDate not supplied

Radiographic evaluation of pulmonary fibrosis following mantle field irradiation in Hodgkin's disease.

Sixty-nine patients given mantle field radiation therapy for Hodgkin's disease and considered relapse-free and possibly cured were re-examined for pulmonary fibrosis as observed on antero-posterior and lateral chest radiographs. A method is described for the systematic evaluation of these late stage changes, which are observed following irradiation, in a numerical form. The method gave reproducible results in this series, the correlation coefficient being 0.72/0.81 and 0.73 respectively for the intra-observer and the inter-observer variations. The method thus may facilitate comparison between different patient materials.

Adult↗
PubMedDate not supplied

Chromosome abnormalities, cellular DNA content, oncogene amplification and growth pattern in agar culture of human neuroblastomas.

The association of ability to grow in vitro, non-random chromosome abnormalities, DNA ploidy and oncogene amplification with prognosis may lead to a better understanding of the biology of neuroblastomas. In a pilot study fresh tumour tissue was obtained from 4 consecutive patients at the Department of Paediatric Surgery, Rigshospitalet, Denmark. Chromosome abnormalities were detected in 3 out of 3 successfully karyotyped tumours, and one or more aneuploid stem lines were detected in 4 out of 4 tumours using flow cytometry. The N-myc oncogene was amplified in 1 out of 3 tumours tested. Continuous cell lines could be established from all 3 advanced stage tumours. This pilot study has shown that fresh tumour tissue can be obtained and successfully studied for various fundamental aspects of the biology of neuroblastomas.

Agar↗
PubMedDate not supplied

Simultaneous meningeal and testicular lymphoblastic transformation of Ph1-positive chronic myelocytic leukaemia in a three-year-old boy.

A three-and-a-half-year-old boy presented in the blastic phase of chronic myelocytic leukaemia (CML) with lymphoblastic infiltration of CNS and testes. The clinical signs and symptoms and also blood and bone marrow findings were otherwise compatible with the chronic phase of the disease, and none of the factors predictive of early transformation were present. Cytogenetic analysis revealed that the Ph1 chromosome, with no additional chromosomal abnormalities, was present in 85% of the bone marrow cells. Meningeal leukaemia is almost unknown in the chronic phase of CML. However, the incidence in the blastic phase may resemble the incidence of CNS leukaemia at diagnosis in children with acute leukaemias. Testicular involvement appears to be extremely rare even in the blastic phase of CML; the "true" incidence may, however, also resemble that of acute leukaemias. This raises the question of the need for testicular and meningeal surveillance and prophylaxis, at least during the blastic phase of CML. One should consider whether the simultaneous meningeal and testicular lymphoblastic leukaemia in this patient was the result of blastic transformation at two independent sites, or whether the testes were seeded from the meninges without identifiable spread to blood and bone marrow.

Antigens, CD↗
PubMedDate not supplied

Response to multimodal treatment in advanced neuroblastomas. Factors associated with complete remission induction, and factors associated with prolonged survival.

The influence of patient and treatment variables upon the probabilities of response to chemotherapy in advanced neuroblastomas was investigated in 71 children with stages III-IV disease treated in Denmark between 1965-1980. The therapeutic regimens consisted of various combinations of chemotherapeutic agents with or without surgical excision of the primary tumour and irradiation. Complete response (CR) was achieved by 75% of patients in stage III, and another 17% showed partial response. In stage IV 60% responded, 19% with CR. Relationships between patient and treatment variables and the probability of being alive in CR 22 weeks after initiation of the treatment were examined by logistic regression analysis. The probability of CR was not related to age at diagnosis, the addition of an anthracycline to the chemotherapeutic regimens, or to irradiation. Factors related to the maintenance of CR could not be statistically examined due to the small number of complete responders at 22 weeks. Only age below 2 years seems, however, to have positive impact on the response duration. The influence of patient characteristics was further suggested by the result of secondary treatment attempts. 42% of the patients selected for secondary treatment responded, and 17% achieved CR. 1/25 (4%) had survived disease-free for more than 8 years. Factors related to the duration of survival were subsequently examined in the 71 children using Cox's regression analysis. Only children below 2 years of age at diagnosis had survived for more than 8 years. Resection of the tumour at diagnosis, irradiation and the addition of an anthracycline appear not to influence the length of survival in this patient population.

Child↗
PubMedDate not supplied

Why age has independent prognostic significance in neuroblastomas. Evidence for intra-uterine development, and implications for the treatment of the disease.

In an unselected patient population consisting of all cases of childhood neuroblastomas in Denmark from 1943 to 1980, evidence was found for the theory that almost all childhood neuroblastomas are congenital, and that the age at diagnosis reflects the duration of the disease, whereas the clinical stage at diagnosis is a result of the growth rate of the tumor and the duration of the disease (i.e. age at diagnosis + up to 9 months). Furthermore, the age at diagnosis may be a measurement of the possibility of micrometastases in addition to the clinical extent of the tumor found at that time, and this may explain why age has independent prognostic significance in childhood neuroblastomas. From the concept that tumours develop by a series of changes from a conditioned to an autonomous state, the theory is consistent with the occasional observation of spontaneous regression of tumours in young infants, and the extremely rare observation of this phenomenon in older children. Since not only the tumor burden, reflected both in the clinical stage and the possibility of micrometastases, but also the proportion of cells resistant to antineoplastic drugs well increase with time, the tumour burden should be reduced as fast as possible with surgery and/or aggressive chemotherapeutic schedules if the disease is diagnosed in advanced stages or in patients older than 1 year of age with stage II disease, whereas surgical resection of the tumor appears to be sufficient treatment for stage I disease and stage II disease of infancy. A consequence of this theory that almost all childhood neuroblastomas are congenital is that screening procedures for the tumour should be carried out as shortly after birth as possible, the expected incidence of congenital neuroblastoma being 1 per 12-14,000 live births.

Age Factors↗
PubMedDate not supplied

Signs, symptoms, metastatic spread and metabolic behavior of neuroblastomas treated in Denmark during the period 1943-1980.

The clinical manifestations of 253 neuroblastoma cases in childhood, treated in Denmark from 1943 to 1980, were reviewed. Most striking was the vagueness of symptoms in the majority of patients, only a few of whom exhibited the symptoms strongly suggestive of a neuroblastoma (i.e. the Horner syndrome, the watery diarrhoea syndrome, the dancing eye syndrome). The vagueness of the symptoms might have led to fatal procrastination of the diagnosis. The diagnostic delay has, however, no independent prognostic significance for survival in our patients (p = 0.09). The maximal tumour spread was recorded for all 253 patients, and the distribution of metastases was in accordance with the "soil-seed" hypothesis. The tumour spreads with equal frequency by local growth, by lymphatic vessels to distant lymph nodes, and by blood to bone. Only in widely disseminated tumours are metastases to the lungs, the meninges, the brain, and the reproductive organs seen to occur. Eighty-five percent of the patients, for whom data were available, excreted VMA above the normal value for their age, and 43% excreted Norepinephrine + Epinephrine (N + E) above normal levels. The excretion of both VMA and N + E was significantly correlated to stage, and thus to prognosis. Neither the level of VMA excretion nor the level of N + E had any bearing on the survival when age and stage were adjusted for. Serial VMA and N + E determinations show that patients with normal values for these parameters had significantly better prognosis than patients with elevated values during the first, second, third and fourth trimesters after the initiation of treatment. Increasing values in the individual patient were associated with a poor prognosis. We found no correlation between the initial leucocyte count and survival when age and stage were adjusted for.

Age Factors↗