Factors that influence the further survival of patients who survive for five years after the diagnosis of cancer in childhood or adolescence

To evaluate the further survival, and to identify disease and treatment factors which influence the further survival, of five-year survivors of cancer diagnosed during childhood or adolescence, we reviewed the courses of 591 previously untreated patients who were less than 20 years of age at diagnosis and survived for five years after diagnosis. Fifty-three of 143 patients who experienced disease recurrence during the first five years after diagnosis died during the period of observation, compared to 18 of 448 patients who did not experience disease recurrence during the first five years after diagnosis. The sex-specific standardized mortality ratios for the group of patients who never relapsed or relapsed more than five years after diagnosis were not significantly different from those of the New York State population. Cox proportional hazards modelling of the subgroup of patients who relapsed during the first five years after diagnosis demonstrated that disease which was treated surgically, a diagnosis of Hodgkin's disease or acute lymphoblastic leukemia, and older age at diagnosis were significantly associated with further survival in this group, whereas similar modelling of the patients who did not experience disease recurrence during the first five years after diagnosis failed to identify any variables which were associated with continued survival. The results of this study suggest that childhood and adolescent cancer patients who survive for five years without disease recurrence have a survival rate similar to that of the general population. Continued follow-up of this cohort is required to determine if the present findings can still be demonstrated as the majority of the cohort ages beyond 35 years of age. © 1994 Wiley-Liss, Inc.     

An update on prostate cancer research

The pathogenesis of prostate cancer reflects complex interactions among environmental and genetic factors. Recent advances suggest molecular mechanisms that may explain geographic and ethnic variations in prostate cancer incidence, and understanding of molecular disease progression is advancing rapidly. Clinically, the case for screening has become stronger, and declining prostate cancer mortality rates may be due in part to early detection and treatment. Improved risk assessment for patients with localized disease is now available, although further refinement in predictive algorithms will need to incorporate validated molecular prognostic markers. Treatment options for patients with localized prostate cancer have expanded and the role of androgen deprivation further delineated. Finally, treatment strategies for patients with androgen-independent disease have also expanded, although novel therapies are required to improve survival in this group of patients.     

Induction of hyperplasia and its suppression by hydrocortisone in organ-cultured rat urinary bladder

Urinary bladders from Fischer rats organ cultured in a chemically defined medium, Ham's F12, underwent transitional cell hyperplasia which persisted for the duration of the culture period (10 days). The hyperplastic response was initiated at 2 days of culture in basal epithelial cells as evidenced by [3H]thymidine autoradiography. After 2 days, cells classified as intermediate cells were observed replicating DNA in increasing numbers, whereas the frequency of basal cells replicating DNA decreased. The peak periods of basal and intermediate cell DNA replication were at 2 and 5 days, respectively. The total increase in the number of cells in the epithelium during a 10-day culture period was approximately 2.6-fold. The appearance of DNA-replicating cells before the appearance of mitotic figures indicated that the cells of the transitional epithelium are primarily G1 cells, The hyperplastic response in the transitional epithelium was significantly inhibited by hydrocortisone. Epithelia cultured in the presence of hydrocortisone also displayed less atypia than those epithelia cultured in its absence. Hydrocortisone concentrations of 2.1 and 21 micronM inhibited hyperplasia by 75 and 84%, respectively, Cells replicating DNA at 2 days of culture were considerably less sensitive to the hydrocortisone inhibition of [3H]thymidine incorporation into DNA than cells replicating DNA at 4 days of culture. The possibility is discussed that basal and intermediate cells may have different sensitivities to hydrocortisone.     

Effect of insulin-induced hypoglycemia on the serum concentrations of thyroxine, triiodothyronine and reverse triiodothyronine

The effect of insulin-induced hypoglycemia on serum thyroid hormone concentrations was studied in nine healthy individuals. Before, during and after the hypoglycemia blood samples were taken for measurement of the concentrations of glucose, thyroxine (T₄), triiodothyronine (T₃), reverse triiodothyronine (rT₃), catecholamines and pituitary hormones.

There was no change in the mean serum T₄ level (± the standard error of the mean) of 67 ± 2 μg/l. However, the T₃ concentrations rose from a mean basal level of 1.86 ± 0.06 μg/l to a mean peak of 2.51 ± 0.21 μg/l (P < 0.01) at 45 minutes after the insulin injection, and the rT₃ concentrations fell from a mean basal level of 0.184 ± 0.008 μg/l to a mean nadir of 0.171 ± 0.022 μg/l (not a significant change). The mean peak epinephrine level was 545 ± 103 ng/l and it occurred between 30 and 45 minutes after the insulin injection; the mean peak norepinephrine level was 584 ± 114 ng/l and it occurred between 30 and 90 minutes after the injection. The growth hormone levels reached a mean peak of 26.1 ± 4.8 μg/l and the plasma cortisol levels rose to 215 ± 9 μg/l. The mean basal prolactin level was 8.5 ± 0.9 μg/l; in five subjects there was a rise to a mean peak of 50.6 ± 14.6 μg/l, whereas in the remaining four no significant increase occurred. No correlation was found between the changes in the serum T₃ concentration and any of the other factors studied.

It was concluded that acute hypoglycemia is associated with a rapid increase in the serum T₃ concentration.

     

Homocytotropic antibody function in the mouse: Eosinophil responses,complement-altering agents and eosinophilia,anaphylactic sensitization

Cellular contents of peritoneal washings were quantitated at 6, 24, and 48 hour intervals after passive sensitieation and antigenic challenge with egg albumin (EA) in CFW strain mice. Control study with heterologous species-precipitating and reaginic rabbit antisera was not possible since injections of normal serum also effected peritoneal eosinophilia and it was found to contain naturally occurring heterophil antibody for mouse erythrocytcs. Significant eosinophil accumulations were demonstrated with immune systems related two homologous species-homocytotropic antibody preparations characterized by 4 hours (IgG₁) and 72 hours (≈ IgE) passive cutaneous anaphylaxis (PCA) properties, respectively. These effects were both blocked in the presence of precipitating antibody (predominantly IgG₂) and minimized under experimental conditions unfavorable for cell fixation of homocytotropic antibody. Lesser degrees of eosinophilia were noted in passive sensitization experiments involving (1) soluble antigen-antibody complexes and (2) precipitating antiserum, and with preparations of EA alone when the contents of molecular aggregates were not reduced by ultrafiltration. There were no significant differences noted in comparably sensitized and challenged animals concomitantly treated with cobra venom factor (CVF) to affect the complement cascade at or beyond C3. While significant diminution in peritoneal eosinophilia resulted from associated treatment with fumaropimaric acid (FPA), biologic effects of this agent other than those involving complement could not be ruled out. Lesser degrees of eosinophilia associated with preformed soluble antigen-antibody complexes, molecular aggregates of antigen, and passive sensitization involving precipitating antibody were lessened by treatment with both CVF and FPA. During the course of these passive sensitization-challenge experiments, the uniform development of anaphylactic shock with 50 per cent incidence of fatal outcomes (SD₅₀) occurred after injections of the immune reactants in a dosage range of 0.1 to 0.2 ml. of 1:64 titer 4 hour PCA homocytotropic antibody reflecting an IgG₁ content of 380 to 860 μg IgG₁ and 250 μg-1.5 mg. EA. Anaphylactic sensitization was not observed in mice passively immunized with either 72 hour PCA homocytotropic antisera (≈ IgE) or precipitating antibody (predominantly IgG₂) and was not enhanced by concomitant treatment with Bordetella pertussis vaccine. Within the limits of these experiments in a mouse model, immune related eosinophilia associated with homocytotropic antibody action was not complement-dependent, and anaphylactic sensitization was identified as a function of IgG₁ but not IgE.     

Cryptococcosis of the larynx.

An unusual case of cryptococcosis of the larynx initially developed as an acute upper airway obstruction that necessitated tracheostomy. Concomitant findings were tracheobronchial ulcerations and edema with severe mainstem bronchial constriction on the left side. Budding "yeast-like organisms" that were consistent with Cryptococcus neoformans appeared in tissue specimens. Epithelial changes that were consistent with pseudoepitheliomatous hyperplasia occurred in areas in the immediate vicinity of the organisms. Sputum and bronchial washing cultures grew nonmycelial, mucinous, encapsulated forms that were positive to staining with mucicarmine and Alcian blue. Treatment with amphotericin B resulted in resolution of the laryngeal obstruction, permitting decannulation. Follow-up direct laryngoscopy and biopsy three months after completion of therapy revealed only mild edema of the false vocal folds. No organisms were found in the tissue, and the pseudoepitheliomatous hyperplastic mucosal changes had resolved.