RESUMEN
Primary malignant epithelial tumors of the liver (PMETL) are rare in the pediatric age group, and very little is known about their biology as compared with adult tumors. The prognostic value of the DNA contents measured by image analysis and expression of oncogene c-erb2 and tumor suppressor gene p53 were studied in 30 cases of PMETL in children, including 24 with hepatoblastomas (HB) and 6 with hepatocellular carcinomas (HCC). p53 overexpression was detected in 12 out of 26 cases (46.0%), or in 3 of 5 HCC and 9 of 21 HB cases. A relatively high concordance of staining was observed with the two antibodies used (clone DO7, Dako and clone DO1, Santa Cruz Biotechnology). c-erb-B2 did not yield the characteristic membrane staining in any of the 27 cases in which reliable staining was obtained. However, 1 out of 4 patients with HCC and 1 of 23 with HB revealed strong granular cytoplasmic staining in several neoplastic cells. Interestingly, these were two of the three aneuploid multiploid cases. DNA histograms of 13 out of 29 cases (54.8%) were classified as DNA aneuploid (5/6 HCC and 8/23 HB): nine were hyperdiploid, one was hypodiploid (1HB), and three were multiploid (2HB and 1HCC). In the HB group, DNA aneuploidy was strongly associated with embryonal histological areas, suggesting that a disturbance in the process of cell differentiation is associated with marked genetic aberrations. Only the group of HB was submitted to univariate analysis of survival by the Kaplan-Meier method for age (< 24 months vs. > or = 24 months), sex, preoperative chemotherapy (yes vs. no), residual disease (metastasis, and/or unresectable tumor), p53 expression by immunohistochemistry (positive vs. negative), and DNA ploidy (diploid vs. aneuploid). Only residual disease at the time of diagnosis (P < 0.017) and preoperative chemotherapy (0.030) were found to be negatively correlated with biological behavior, estimated as overall survival. DNA aneuploidy tumors (P < 0.125) and male patients (P = 0.123) showed a trend toward a more aggressive clinical behavior, although the difference was not statistically significant. Combining DNA ploidy and residual disease, patients were categorized into three groups: group I, patients with no adverse prognostic factors, i.e., diploid tumors without residual disease; group II, patients with only one adverse prognostic factor, i.e., aneuploid tumor or residual disease; and group III, patients with both adverse factors, aneuploid tumors and residual disease at time of diagnosis. A log-rank test comparing the three survival curves showed a statistically significant difference between them (P < 0.003). Although the series of cases is small, the results of this study highlight the importance of including DNA ploidy in the protocols designed for HB in children by international cooperative groups.
Asunto(s)
Carcinoma Hepatocelular/genética , ADN de Neoplasias/análisis , Regulación Neoplásica de la Expresión Génica , Hepatoblastoma/genética , Neoplasias Hepáticas/genética , Oncogenes/genética , Adolescente , Niño , Preescolar , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Ploidias , Pronóstico , Receptor ErbB-2/biosíntesis , Receptor ErbB-2/genética , Estudios Retrospectivos , Análisis de Supervivencia , Proteína p53 Supresora de Tumor/biosíntesis , Proteína p53 Supresora de Tumor/genéticaRESUMEN
PURPOSE: To evaluate the disease-free and overall survival of pediatric patients with nonrhabdomyosarcoma soft-tissue sarcomas. METHODS: We retrospectively analyzed the records of 67 pediatric patients with a diagnosis of nonrhabdomyosarcoma soft tissue sarcoma treated with curative intent between 1970 and 1992. Median follow-up time for the 52 survivors was 120 months (range, 7 to 277 months). Fifty-nine patients received external beam radiotherapy, in a median dose of 5400 cGy (range, 1800 to 6660 cGy.) All patients underwent an initial surgical procedure. Eighteen patients had gross residual disease, and 15 had gross total excision with microscopic residual disease or positive margins. Adjuvant chemotherapy was administered to 44 patients (65%). RESULTS: The actuarial 10-year freedom from progression or recurrence and overall survival rates were 76% and 75%, and the 20-year rates were the same. Of 18 patients with gross residual disease, 9 (50%) had local progression and 6 died of local-only disease. By contrast, only one patient with microscopic residual disease who received postoperative radiotherapy had a local recurrence. The disease-free survival rate also correlated with histologic grade. CONCLUSIONS: As with adult soft tissue sarcomas, gross residual disease predicts local failure. Our results suggest that pediatric patients with soft tissue sarcomas treated with surgery and postoperative radiotherapy generally have a favorable overall survival rate.
Asunto(s)
Sarcoma/mortalidad , Neoplasias de los Tejidos Blandos/mortalidad , Adolescente , Adulto , Quimioterapia Adyuvante , Niño , Terapia Combinada , Femenino , Estudios de Seguimiento , Humanos , Masculino , Recurrencia Local de Neoplasia , Estudios Retrospectivos , Sarcoma/tratamiento farmacológico , Sarcoma/radioterapia , Sarcoma/cirugía , Neoplasias de los Tejidos Blandos/tratamiento farmacológico , Neoplasias de los Tejidos Blandos/radioterapia , Neoplasias de los Tejidos Blandos/cirugía , Tasa de SupervivenciaRESUMEN
OBJECTIVE: To describe the clinical, laboratory, and histopathologic features of idiopathic steatohepatitis in children. STUDY DESIGN: Retrospective review of all liver biopsies performed at Boston Children's Hospital, Massachusetts General Hospital, and the University of Massachusetts Medical Center from 1991 to 1994. Chart review was performed when biopsies demonstrated steatosis. RESULTS: Eighty-two patients had biopsy-proven hepatic steatosis. Fourteen patients had fatty liver without evidence of inherited, infectious, autoimmune, endocrinologic, toxicologic, or iatrogenic causes. All 14 patients were obese, averaging 159% of ideal body weight (range, 121% to 222%). Nine patients initially had transient abdominal pain, two had hepatomegaly, and one was identified by incidental laboratory evaluation. These 12 patients had biopsies because of persistent elevations of aminotransferase levels. Two other patients without risk factors for steatosis were identified at staging laparotomy for Hodgkin lymphoma. The 10 boys and 4 girls had an average age of 13.5 years (range, 10 to 18 years). Aminotransferase elevations were modest, with aspartate aminotransferase and alanine aminotransferase values averaging 77 +/- 38 IU and 129 +/- 73 IU, respectively. All had imaging studies demonstrating diffuse fatty change. Histologic examination of biopsy specimens revealed varying degrees of steatosis with inflammation and fibrosis. CONCLUSION: Idiopathic steatohepatitis occurs predominantly or exclusively in obese peripubertal children. This entity represents a frequent reason for liver biopsy in this age group. The degree of steatosis, fibrosis, and inflammation does not correlate with symptoms or signs, and significant liver injury with bridging fibrosis may be present.