Biomedical subjects
Publications and source records attributed to J Lemerle.
A 4 year-old child being treated for neuroblastoma developed erythroblastopenia. We used specific erythroid lineage markers (hemoglobin and spectrin) and in vitro erythroid colony assays to characterize this hematologic picture and discuss its relationships with the disease and its treatment.
Treatment of medulloblastoma in children with head and spinal irradiation causes growth hormone deficiency and growth retardation. The present study deals with 45 patients presenting a follow-up time superior to 4 years; some of them having reached their final height. The mean final height is 3 standard deviations below normal mean. Growth retardation which occurred in 42 of 45 children, appears to be due to two major factors: 1) GH deficiency in 42 cases as assessed by the arginine insulin tolerance test. 2) Spinal lesions due to irradiation, causing early growth retardation and a reduced trunk length in most of these children. The response to hGH treatment (10 mg/kg/yr) was not sufficient in this group of patients.
Unusual clinical, radiologic, or histologic findings were found in 11 of 17 cases of hypercalcemia associated with childhood tumors. Four children had undifferentiated lymphoblastic lymphoma with extensive bone involvement, but no visceral or neurologic involvement. At diagnosis, four adolescents with rhabdomyosarcoma had numerous metastases, particularly in the breasts and bone marrow. Three infants had renal tumor without bone metastases. Histologically, their tumors differed from classical nephroblastoma and resembled the malignant rhabdoid tumors of the kidney. These findings allow individualization of three distinct groups of tumors with unusual features which may suggest the presence of hypercalcemia. These tumors appear to have a poor prognosis since all patients but one died of their malignancy.
Thirty-five children with Stage III and IV nonseminomatous malignant germ cell tumors were treated, between June 1, 1977 and December 31, 1982, at Institut Gustave-Roussy, Villejuif, France, and Hospital General de Ninos, Buenos-Aires, Argentina: 11 sacrococcygeal, 12 ovarian, 6 testicular, 5 intrathoracic, and 1 intrabdominal site. All of them had yolk sac component with high level of AFP, seven had also elevated level of HCG. Thirteen patients had primary chemotherapy, 18 received chemotherapy after incomplete surgical excision, and 4 patients with testicular Stage III tumors had chemotherapy immediately following retroperitoneal lymphadenectomy after orchiectomy, because of persistently elevated AFP levels. The chemotherapy regimen for 1 year's duration, repeated every 21 days, and consisted of 6 courses of dactinomycin-Cytoxan (cyclophosphamide) D1 to D5 and vincristine, Adriamycin (doxorubicin) D21, bleomycin D23, and cisplatin D24. Only three patients received complementary radiotherapy. The toxicity of the chemotherapy regimen was severe, but only one death was due to the therapy (pulmonary fibrosis with bleomycin). The number of surviving patients without evidence of disease was 12 of 16 for Stage III and 12 of 19 for Stage IV. The 25-month survival rate was 63% with a follow-up of 11 months to 5.5 years (median, 22 months). This constitutes a dramatic improvement when compared with the survival rate of 21% of 48 similar patients treated at Institut Gustave-Roussy between 1968 and 1977 with surgery, radiotherapy, and chemotherapy (methotrexate, dactinomycin, and Cytoxan).
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From April, 1978 to December, 1982, 87 cases of Ewing's sarcoma were registered in 12 centres of paediatric oncology in France. The results of a therapeutic protocol consisting of intensive chemotherapy (vincristine, cyclophosphamide and actinomycin with or without adriamycin) prior to tumoral irradiation, followed by maintenance chemotherapy are reported after 3 years' follow-up from the beginning of treatment. In localized sarcomas, complete remission (66/70) persisted without relapse or metastasis in 54% of the cases (78% in sarcomas of long bones, and 37% in sarcomas of short bones). In non-metastatic sarcomas of the ribs, the first remission persisted in 7/14 patients (50%). All these patients had been initially treated with chemotherapy, radiotherapy and surgical excision. These preliminary results emphasize the value of co-operative therapeutic trials in a rare tumour, demonstrate the effectiveness of the initial chemotherapy used against Ewing's sarcoma and are in favour of a combined treatment, including systematic excision, for Ewing's sarcomas affecting the ribs.
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Sixteen children with non-Hodgkin's lymphoma (NHL) who had relapsed were treated with high-dose chemotherapy with BCNU, cyclophosphamide, cytarabine, 6-thioguanine (high-dose chemotherapy [HDC]) and autologous bone marrow transplantation (ABMT). Eleven complete responses were obtained and five patients remain in prolonged complete unmaintained remission 77+ to 152+ weeks after treatment. The best results were obtained in patients with CNS involvement and when this regimen was used after complete remission or partial response was obtained by other means. The results appear to be better in B-cell than in T-cell lymphomas, but the numbers are too small for statistical assessment. The use of ABMT rendered the pancytopenic period short and safe, despite the use of drug doses higher than those previously described for this HDC. The frequency of interstitial pneumonitis, possibly related to pulmonary toxicity of chemotherapy, remains a major concern. These results show that this regimen can help to cure some patients but its toxicity prohibits its use in primary therapy.
Multiple Endocrine Neoplasia type 2b (MEN 2b) is a rare syndrome. The principal features are: medullary thyroid carcinoma (MTC), dysmorphism, a ganglioneuromatosis and pheochromocytomas. Eight cases of MEN 2b have been observed at the Institute Gustave Roussy, between 1968 and 1983. Seven involved children under 15 years of age. Eight had a bilateral MTC; six had dysmorphism; six had mucosal tongue neuromas. Six were troubled with visceral ganglioneuromatosis of whom two had intestinal obstruction and one urinary chronic retention. One patient had pheochromocytoma with hypertension. From this experience and other data it appears that: the dysmorphism is frequently poorly interpreted; the visceral ganglioneuromatosis is an early and severe feature; it is important to examine the patient for pheochromocytoma; the MTC must be detected by calcitonin dosage after stimulation, and requires total thyroidectomy; familial screening must be done. To improve the poor prognosis of MEN 2b, early diagnosis and aggressive treatment are necessary.
Thirty-eight children, followed in the pediatric Department of Institut Gustave-Roussy, developed second malignant neoplasms. Intervals between the two neoplasms ranged from 1 to 26 years. The second neoplasms were defined as having a different histologic diagnosis than the first ones: osteosarcoma, fibrosarcoma, thyroid carcinoma, leukemia were the most frequent second neoplasms. The potential carcinogenic part of chemotherapy and radiotherapy is emphasized. In addition, some genetic susceptibility may enhance the carcinogenic effects of therapy. Nevertheless the incidence of second malignant neoplasms is low. Its estimation is discussed here.
Thirty episodes of hypercalcemia were observed in 20 children with solid tumors: principally 9 cases of non Hodgkin's lymphomas, 4 cases of rhabdomyosarcomas and 4 cases of Wilms' tumors. The 2 children with neurological manifestations and hypertension had the most severe symptoms secondary to the high calcium levels. However, hypercalcemia was asymptomatic in 8 of the 20 children. Focal seizures and metastatic calcifications subsequently occurred in 6 children. Emergency treatment of hypercalcemia often had partial or transient efficiency. In contrast, high calcium levels always returned to normal after anti-tumoral treatment.
Acute haemorrhagic pancreatitis developed in a 12 year old boy treated for lymphoblastic lymphoma. No etiological factor could be identified, except for asparaginase. Although the condition was initially severe, the patient recovered. Regular CT monitoring demonstrated the formation of a pseudocyst in the pancreatic tail which spontaneously regressed without complications.
The results of a controlled clinical trial of preoperative radiotherapy compared to chemotherapy in patients with nephroblastoma are presented. Of 397 histologically proven cases of Wilms' tumor registered at 34 centers between January 1977 and July 1979, 164 were eligible for the trial and were randomized to receive preoperative radiotherapy and chemotherapy (group R, 76 patients) or preoperative chemotherapy (group C, 88 patients). The results were evaluated in terms of the number of surgical tumor ruptures and of local tumor extent at pathologic examination, reflecting the effectiveness of the preoperative treatment. Survival and recurrence-free survival in the two treatment groups were also taken into account. The stage distribution was comparable in the two groups, with 52% stage I tumors in group R, and 43% in group C. Significant changes in the pathologic pattern were more frequent in group R than in group C (53% versus 17%). From these data it is concluded that preoperative chemotherapy is as good as preoperative radiotherapy in terms of prevention of tumor rupture. In addition, it was shown that 43% of an unselected population of patients with Wilms' tumor could be treated without any radiotherapy when chemotherapy had been given preoperatively.
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The analysis of the health risks associated with the administration of diethylstilbestrol (DES) during pregnancy (for the prevention or treatment of threatened abortions) has been largely published. Concerning mothers, a relationship between DES exposure during pregnancy and risk of cancer is unproved. However, existing studies are sufficient cause for serious concern over drug's carcinogenic potential, and further follow-up studies are required. Concerning daughters, a clear association between in utero exposure to DES and clear cell adenocarcinoma of the vagina or cervix is established (incidence between 0.14 and 1.4 per 1000 through age 24). The risk for squamous cell cancer of the vagina and cervix does not seem to be increased. Cervico-vaginal adenosis is frequent (20% to 60% of exposed subjects). This is not a pre-cancerous lesion, its spontaneous evolution is towards regression. No treatment is prescribed. Morphological changes of the genital tract have been described, their consequences on fertility and pregnancy are not clear. Concerning sons, an excess of genital abnormalities (especially of the epididymis and undescended testis) has been reported, but information on the fertility implications of these findings is not available. There is no evidence of an increased risk of testicular cancer. The analysis of all these informations should allow to bring up a policy to take into account these risks in the population.
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Eleven infants were treated at the Institut Gustave-Roussy between 1967 and 1980 for a yolk sac tumor localized to vagina. All the children had high serum alpha-foetoprotein levels. The average age was 10 months and the first symptoms were vaginal hemorrhages. The volume of the tumor and tumoral extension, as well as the biopsy, were appreciated by vaginal examination under general anesthesia. Treatment fluctuated during these years; 7/11 children were cured and since 1977, 6/8 (average follow-up 3 1/2 years) with the following therapeutic schedule: primary chemotherapy reducing the tumoral volume, and either partial colpectomy or curietherapy or both. So, these 6 girls were cured with a conservative treatment, preserving uterus and vagina. Two of them had moderate sequelae due to curietherapy.
From 1975 to 1979, 173 children with neuroblastoma were treated according to the same protocol at the Institut Gustave-Roussy. They were classified according to the site of the primary tumor (abdominal: 122; thoracic: 29; others: 22) and according to TNM staging (stage I: 8; stage II: 24; stage III: 35; stage IV: 99; stage V: 2). Depending on stage and age, treatment consisted of surgery and radiotherapy associated with cyclic multiagent chemotherapy (vincristine, Adriamycin, cyclophosphamide). It resulted in a significant improvement of prognosis in stage III patients, especially those with abdominal tumors. In the latter group, prognosis depended mainly on the possibilities of resection of the tumors. Therefore, making these tumors operable remains the major goal of therapy in such patients. Radiotherapy is quite efficient in sterilizing the small post-surgical residual tumors. Prognosis in children over 1 year of age with metastases still remains very poor, even though the quality of the survival is improved.