The contribution of salvage surgery to the management of childhood osteosarcoma.

Between January 1970 and December 1988, 174 consecutive patients under the age of 20 years with curatively resected primary osteosarcoma were treated at our institute; 72 in the years of 1970 to 1981 and 102 in the years 1982 to 1988. In the latter period, adjuvant chemotherapy was replaced by neoadjuvant programs, and new criteria were adopted for the management of lung metastases, consisting in early bilateral surgical staging and lung resection through median sternotomy for all patients with purely intrathoracic relapse. Follow-up was updated in December 1989. During the last period, the overall 5-year survival improved significantly from 35% to 58% (P less than .001). The disease-free survival rose from 38% to 45% at 5 years, with median values of 15 months versus 33 months, while the frequency of isolated lung metastases dropped from 58% to the actuarial 48%. The proportion of patients who underwent complete resections of their pulmonary metastases rose from 17% (seven of 42) to 55% (27 of 49), without operative mortality. Due to such a high proportion of patients eligible for salvage surgery, the overall survival from detection of lung metastases improved from 0% to 28% at 5 years (P less than .001). Contralateral occult metastases were resected in three of 15 subjects with monolateral clinical lesions, and five patients underwent subsequent lung resections. These data indicate that systematic bilateral pulmonary resection plays an important role in improving the final cure rate of childhood osteosarcoma, beyond the benefit resulting from neoadjuvant chemotherapy.

Germ cell tumors of the ovary: the experience of the National Cancer Institute of Milan. I. Dysgerminoma.

The experience of the Istituto Nazionale Tumori of Milan on dysgerminoma is presented. Between 1970 and December of 1982, 25 patients were treated with a unique protocol which considered surgery and radiotherapy with different schedules according to the extension of the disease. With this treatment protocol all 13 patients at Stage I were alive and free of disease with a median follow-up of 77 months. Of 12 patients at Stage III (10 retroperitoneal and 2 retroperitoneal and peritoneal) 4 relapsed. The 5-year relapse-free survival of Stage III patients was 61.4% and the overall survival 89.5%. Amenorrhea due to radiation dose absorbed by the contralateral shielded ovary was found in 7.7%. The excellent results in Stage I patients were balanced by the unsatisfactory results in Stage III patients. A more aggressive treatment and the knowledge of other prognostic factors seem necessary.

Restatement of lymphography in childhood: experience with 413 consecutive patients in ten years.

From January 1969 to June 1978, 413 children under 15 years of age underwent lymphography at the Istituto Nazionale Tumori of Milan. Successful lymphatic cannulation was accomplished in 97.7% (769/787) of the sites where it was attempted. No major or permanent complications were encountered. In those children undergoing biopsy of opacified lymph nodes, the lymphographic-histologic correlation was 94.5% (104/110). This study has shown that lymphography in childhood can be as readily performed as in the adult and that its diagnostic accuracy is acceptable. As in adults, it is useful in treatment planning, evaluating results of therapy, and detecting a recurrent tumor.

Lymphography in childhood: six years experience with 242 cases.

From January, 1969 - December, 1974, 242 children less than 15 years of age underwent lymphography at the National Cancer Institute, Milan. Successful lymphatic cannulation was accomplished in 97% (440/463) of the sites where it was attempted. No major or permanent complications were encountered, although minor untoward effects might not have been recorded. In those children undergoing biopsy of opacified lymph nodes, lymphographic-histologic correlation was 98% (45/46). Nonspecific reactive hyperplasia lymphographic patterns were encountered in 36% of all studies, confirming its high incidence in the pediatric age group. This study has shown that lymphography in childhood can be as readily performed as in the adult and that its diagnostic accuracy is acceptable. As in adults, it is useful in treatment planning, evaluating results of therapy, and detecting recurrent tumor. The frequent occurrence of nonspecific reactive hyperplasia in the pediatric lymphogram should not be mistaken for evidence of tumor, particularly lymphoma.

Liver tumors in childhood: epidemiology and clinics.

Childhood liver tumors have received great attention for many reasons: their vast histologic variety, uncertainty about pathogenesis and classification, recent gains in genetic understanding, relationship to antecedent diseases, and difficulties in treatment. In this paper we review the main epidemiological aspects of malignant epithelial and nonepithelial liver tumors of children, clinical aspects at presentation of disease, and diagnostic evaluation with biological and imaging studies.

Radiographic findings in previously untreated children with non-Hodgkin's lymphoma.

The initial radiographs of 51 consecutive, previously untreated children with non-Hodgkin's lymphoma were reviewed. The chest radiograph was abnormal in 37%, with pleural effusions seen in 14% of patients. Lymphography, readily performed in children, was positive in 30% of the successful studies. There was a high incidence of bone lesions (18% of patients), due in large part to involvement of the facial bones; all were symptomatic and/or seen on the routine chest and abdominal radiographs. Intrinsic disease of the small bowel (10%) and colon (8%) was also associated with symptoms, so that the value of routine barium studies in asymptomatic children is questioned.

Childhood non-Hodgkin's lymphoma: long-term results of an intensive chemotherapy regimen.

Twenty-nine consecutive children with untreated non-Hodgkin's malignant lymphoma were admitted to Istituto Nazionale Tumori of Milan during the period from 1974 through 1976 and underwent treatment with chemotherapeutic regimens consisting of Adriamycin, Cytoxan, vincristine, and prednisone (two month induction phase) and 6-mercaptopurine, methotrexate, Adriamycin, vincristine, and prednisone (maintenance phase). Each patient, regardless of clinical stage of histologic subgroup, was given the same chemotherapy. The complete response rate was 66%. Due to the high incidence of recurrence of the initial bulky lymphomatous mass and of spread to the central nervous system (CNS), local radiotherapy was given to ten children and CNS prophylaxis (brain radiotherapy + intrathecal methotrexate) to 11 children. After a follow-up period in excess of 40 months, there were five disease-free survivors (17%). Each patient who had a relapse died from the disease. The main reason for first treatment failure was relapse at the level of the primary bulky tumor site or spread to the CNS. This type of CNS prophylaxis did not prevent relapse at this site.

Medulloblastoma. Results of a sequential combined treatment.

Actuarial progression-free survival rate at 5 years of a series of 34 patients with medulloblastoma treated by combined surgery, radiotherapy, and chemotherapy was 71%. No relapses were observed in 14 patients followed for more than 5 years. Treatment consisted of a short postoperative course of vincristine (VCR) and intrathecal (IT) methotrexate (MTX) followed by irradiation to the entire cranio spinal axis. Maintenance chemotherapy (CCNU, VCR, and IT MTX) was then continued to encompass 2 years from surgery. Failure occurred in nine patients: four had local recurrence, four dissemination within the central nervous system, and one widespread skeletal metastases. Poor prognostic factors such as presence of malignant cells in the cerebrospinal fluid, non-radical surgery, young age, and radiation doses less than 50 Gy to the tumor bed, did not adversely affect the outcome of patients in this series. Long-term sequelae from the treatment program could be observed in all patients, and in 58% they were severe enough to interfere with normal, active life.

Therapeutic approach to primary malignant epithelial tumors of the liver in childhood: results of the Italian retrospective study and literature survey.

We analyzed the clinical features and treatment of 23 hepatoblastomas (HPBs) and 16 hepatocellular carcinomas (HPCs) occurring in patients less than 19 years old, admitted to the Italian retrospective multicentric study, conducted between 1983 and 1985, on childhood malignant hepatic tumors. The median ages of the patients with HPB and HPC at diagnosis were 22.34 months and 96.23 months, respectively, with a male/female ratio of 0.7 and 1.7, respectively. Fourteen HPBs (61%) and 5 HPCs (31%) achieved surgical complete remission (CR). Of these, 11 HPB and all 5 HPC are still in CR with a median follow-up of 36 months and 3.5 years, respectively. One HPB and 1 HPC became resectable after a primary course of cis-platinum alone in the case of HPB and used with VP-16 in the case of HPC. All of the 9 HPBs and 11 HPCs, who never achieved CR, died of disease at a median interval from diagnosis of 5 and 2 months, respectively. The published therapeutic approaches for these tumors were also reviewed.

Neuron-specific enolase evaluation in patients with neuroblastoma.

Neuron-specific enolase (NSE) may be of interest for the prognostic evaluation and follow-up surveillance in patients with neuroblastoma. We evaluated NSE levels in 80 patients with neuroblastoma. The marker correlated with stage (in stage 1 patients, the median NSE level was 9.9 ng/ml, in stage 2, 45.1 ng/ml, in stage 3, 49 ng/ml, in stage 4, 93.9 ng/ml, in stage 4S, 53.4 ng/ml) and with survival. In patients with a favorable or a poor outcome, the difference in basal NSE serum levels was statistically significant (p = 0.0001). Serial measurements revealed that there was a good correlation between NSE levels and disease course. We concluded that NSE is a good marker for neuroblastoma and its quantitative determination in serum is valuable in the management of these patients to confirm the diagnosis, monitor the effect of treatment and detect recurrent disease.