The effects of serum depletion and dexamethasone on growth and differentiation of human neuroblastoma cell lines.

BACKGROUND/PURPOSE: Neuroblastoma is the most solid common extracranial malignancy in childhood. Despite multimodality treatment, high-risk disease continues to carry a poor prognosis. Glucocorticoids have been shown previously to induce differentiation in murine neuroblastoma cell lines, but no such effect has been documented in human neuroblastoma cells. Glucocorticoids are known to be active in the differentiation process of the neural crest. These studies describe the effects of dexamethasone on 6 human neuroblastoma cell lines. METHODS: Dexamethasone was added to cultured neuroblastoma cell lines (LA1-5S, LA1-15N, BE[2]S, BE[2]N, SH-EP-1, SH-SY5Y) maintained in media supplemented with either normal serum or charcoal-depleted serum. Proliferation assays were performed, and flow cytometry was used to assess alterations in cell cycle. Cells were closely monitored for morphological changes with serial phase-contrast microscopy. Immunohistochemistry (3F8, NF-1, TRK-A) of cultured cells was used to evaluate differentiation. Glucocorticoid receptor levels was assessed using immunoblotting. RESULTS: Dexamethasone decreased the rate of cellular proliferation in both standard and charcoal-depleted conditions. Flow cytometry showed a G1 accumulation. Increased expression of the differentiation-associated antigens was found in cells cultured in charcoal-depleted media, and a further augmentation was seen with the addition of dexamethasone. In standard media, dexamethasone had no detectable effect on the expression of these antigens. Glucocorticoid receptor expression was found to be comparable in all cell lines. CONCLUSIONS: Human neuroblastoma cells are sensitive to the differentiating effects of dexamethasone in an environment of charcoal-depleted serum. This phenomenon may be caused by the existence of growth and mitogenic factors in serum that are inhibiting differentiation.

Kinetics of primary tumor regression with chemotherapy: implications for the timing of surgery.

PURPOSE: The kinetics of tumor regression during administration of chemotherapy has relevance to the timing of surgery. The aim of this study was characterization of the time course of primary tumor regression in initially unresectable rhabdomyosarcoma, hepatoblastoma, and neuroblastoma patients. We also estimated the total cell number in the primary tumor at diagnosis. METHODS: Tumor volumes of 24 pediatric patients with either unresectable rhabdomyosarcoma, hepatoblastoma, or neuroblastoma were determined by using computerized three-dimensional reconstruction from serial computed tomography (CT) scans during chemotherapy. Cell densities were calculated by counting cell numbers in high-power fields and dividing by area and section thickness. Cell number at diagnosis was then calculated. RESULTS: Median tumor volumes at diagnosis were 175 cc, 748 cc, and 738 cc for rhabdomyosarcoma, neuroblastoma, and hepatoblastoma, respectively. The median tumor cell counts were 31, 68, and 59 x 10(10) cells/tumor for rhabdomyosarcoma, neuroblastoma, and hepatoblastoma, respectively. The tumor regression was most rapid during the first two cycles, and little change in volume was observed after three cycles. CONCLUSION: Rapid initial reduction in primary tumor volume with chemotherapy was observed in rhabdomyosarcoma, neuroblastoma, and hepatoblastoma. These data suggest that second-look resection may be feasible after two to three cycles of chemotherapy. This hypothesis may be tested by randomizing the timing of second-look surgical intervention.

Renal cell carcinoma in childhood and adolescence: a retrospective survey for prognostic factors in 22 cases.

To identify prognostic factors for renal carcinoma in young patients, a retrospective analysis was performed of 22 patients (< or = 21 years of age) with histologically verified renal cell carcinoma. Demographic, staging, and treatment variables were collected in a database, and their effect on survival was determined using Kaplan-Meier probability distribution. The median age was 15.5 years (range, 3 to 21 years), and the male:female ratio was 13:9. Only three patients were black. Histopathologic examination showed 15 clear cell tumors, 4 mixed cell type, 2 papillary, and one well-differentiated adenocarcinoma. The median size of the primary tumor was 10 cm (range, 5 to 20). There were seven patients with stage I tumors, one with stage II, and 14 with stage IV. Complete resection of the primary tumor was accomplished in 12 patients. The overall 5-year survival rate was 30% (confidence interval, 20% to 40%). The 5-year survival rate was better for patients who had complete resection of the primary tumor (60% v 10%). Unresectability was associated with involvement of nodes and/or occurrence of metastases, thus an independent effect of complete resection on survival could not be demonstrated. The data showed that age, tumor size, location, and histology were not predictors of outcome; tumor stage and complete surgical resection were the only meaningful prognostic factors. The presentation of renal cell carcinoma as a localized or systemic disease may reflect a twofold biological behavior. In the first group, the disease is curable with resection, in the second, it is unaffected by surgery or adjuvant therapy. In light of the very low incidence of this renal malignancy in childhood, prospective multicenter studies will be required to improve the poor therapeutic results.

Cardiac tamponade in the pediatric oncology population: treatment by percutaneous catheter drainage.

PURPOSE: The treatment of pericardial effusion resulting in cardiac tamponade has undergone an evolution in recent years, with the use of less invasive drainage methods in selected cases. To determine optimal therapy for pediatric oncology patients with pericardial effusion and tamponade, the authors reviewed their institutional experience with percutaneous catheter drainage. METHODS: Patient records and operative reports were reviewed, and nine patients were identified who met clinical and echocardiographic criteria of cardiac tamponade and were treated with percutaneous pericardial catheter drainage. RESULTS: The median age at time of diagnosis was 14 years (range, 5 months to 19 years), and the male:female ratio was 7:3. Underlying malignancies included acute myeloblastic leukemia in three, acute lymphoblastic leukemia in one, and Hodgkin's disease, B-cell lymphoma, medulloblastoma, desmoplastic small round cell tumor, and rhabdomyosarcoma in one each. EIght patients (89%) were receiving granulocyte colony-stimulating factor (GCSF) during the period when tamponade developed. All patients had a large or moderate-to-large pericardial effusion and right ventricular collapse with hemodynamic compromise on echocardiography, and two patients (22%) also had pericardial thickening. In nine patients, percutaneous catheter drainage was performed intraoperatively and under fluoroscopic or echocardiographic guidance. A median of 300 mL (range, 82 to 500 mL) of fluid was removed from the pericardial sac during the initial drainage, and cytology was positive in one (6%). Complete echocardiographic resolution was observed in eight patients (89%); a small posterior component persisted in one patient but was not significant hemodynamically. The catheters remained in place for a median of 5 days (range, 1 to 35 days) while repeat aspirations were performed. Tamponade resolved in all patients, and one died of overwhelming systemic sepsis. The survival period was 10 to 22 months, and tamponade or the drainage procedure did not contribute to death. Four patients remain alive after 4 month to 7 years of follow-up. CONCLUSION: Cardiac tamponade was effectively treated in all patients and did not recur with percutaneous catheter drainage alone. THere was no evidence of pericardial loculation or infection despite pancytopenia being prevalent with underlying illness and chemotherapy. Percutaneous catheter drainage is an effective treatment for pediatric oncology patients with pericardial tamponade. Because of its simplicity in comparison to move invasive techniques, initial treatment with percutaneous drainage should be considered in this patient population.