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.

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.

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.

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).

Pericentric inversion in chromosome no. 2 as a de novo mutation.

A patient with a de novo inversion of chromosome 2 is described. Two of her three children have the same inversion.