Integrating a palliative approach into the healthcare provided by the French-African Pediatric Oncology Group's pilot units. Insights from a 3-year training program.

Working alongside local stakeholders, members of the French-African Pediatric Oncology Group developed a 3-year program to train pediatric oncology teams from 15 French-speaking countries in Africa in using analgesics and providing palliative care. This program was rolled out in three phases: initial training, in situ assessment, and advanced training in selected topics. To access this program, multidisciplinary teams had to come up with a project to improve their existing palliative care and pain management practices, and commit themselves to implementing it. All the teams invited agreed to take part in the program, which explicitly broached a subject that is often avoided in oncology teaching. The first phase was rolled out in 2017, with 65 trainees from 19 units attending one of three sessions held in Dakar, Senegal, Abidjan, Côte d'Ivoire, and Rabat, Morocco. The subsequent assessment revealed that only half the teams had started to implement their projects. The advanced training phase was therefore adjusted accordingly. A collective training session held in Marseille was attended by 15 trainees from seven teams whose projects were already underway, while in situ mentoring was provided for six other teams, through French-African twinnings in four cases. The length and openness of the program meant that we were able to identify and share the units' diverse realities, and fine-tune their projects accordingly, as well as plan ways of continuing the training both locally and collectively.

[Male fertility after chemotherapy during childhood]. / Fertilité masculine après chimiothérapie dans l'enfance.

Chemotherapy has considerably improved the prognosis of solid tumours in children, but may have very adverse effects, particularly on fertility. A study was conducted at the Gustave Roussy Institute to identify the toxic effect of chemotherapy on male fertility. At present, 205 patients, treated during childhood have entered the study. Basal FSH-LH have been assayed to assess possible germ cell damage although azoosperia can not be eliminated. Results were normal in 127 patients (62%) and increased basal FSH levels were found in 78 (38%). Endocrine function was not altered: all patients were either impubertal or intrapubertal at diagnosis and subsequently achieved normal puberty. Multivariate analysis revealed an obvious toxic effect of 2 alkylating drugs: cyclophosphamide and procarbazine. No toxic effect was observed for vincristine, dohorubicin or actinomycin D. Age and pubertal status at diagnosis were not correlated with toxic effects. At present, no conclusion for other drugs may be made but results high dose metotrexate are promising. For lomustine and cisplatin, less favourable, though nonsignificant, results have been obtained. Complete recovery is possible several years later.

Cerebrospinal fluid and plasma methotrexate levels following high-dose regimen given as a 3-hour intravenous infusion in children with nonHodgkin's lymphoma.

In the French nonHodgkin's lymphoma protocols, central nervous system prophylaxis is provided by high-dose methotrexate (HD-MTX), given as a 3-hour IV infusion of 3 g/m2 MTX along with intrathecal MTX injection. The incidence of CNS relapse is less than 3%. We designed a study to evaluate the MTX transfer across the blood brain barrier in terms of cytotoxic concentrations, during these short-term infusions. Cerebrospinal fluid and plasma MTX levels were measured during 61 courses in 29 children with nonHodgkin's lymphoma; none of them had central nervous system disease. Samples were obtained either 4, 12, 18, or 24 hours after the start of HD-MTX IV infusion. A potentially cytotoxic MTX level (10(-6)M) was reached in all courses at 4 hours (median: 2.3 X 10(-6)M) and remained available in 8/16 courses at 12 hours (median: 1.0 X 10(-6)M) and in only 2/17 courses at 18 hours (median: 0.29 X 10(-6)M). Twenty-four hours after the start of HD-MTX IV infusion, CSF MTX level was always less than 10(-6)M. The plasma MTX levels were 260, 1.3, 1.0, and 1.7 X 10(-6)M at 4, 12, 18, and 24 hours, respectively. There was no correlation between plasma and CSF MTX levels. These data show that potentially cytotoxic MTX concentrations can be reached in CSF after a 3-hour IV infusion of 3 g/m2 in every patient and remain available for at least 8 hours in half of them.

Male gonadal function after chemotherapy for solid tumors in childhood.

The testicular function of 30 adolescent or adult males having undergone polychemotherapy in childhood was assessed by means of a spermogram or testicular biopsy. At the time of examination, the patients were pubertal and had completed chemotherapy between 1 and 20 years previously (mean, 9 years). All patients who were prepubertal or intrapubertal at the time of treatment achieved normal puberty with normal growth. Twenty patients presented with azoospermia and/or severe disturbances in the germinal line on biopsy. This series confirms the toxicity of alkylating agents, in particular that of the mechlorethamine, vincristine, procarbazine, and prednisone combination (MOPP) and that of cyclophosphamide (CPM). However, dactinomycin, vinblastine, and vincristine did not appear to have a toxic effect on spermatogenesis. The prepubertal state did not protect the gonads of 19 patients who were prepubertal at diagnosis: 12 are now sterile as a result of the treatment. An increase in basal follicle-stimulating hormone (FSH) levels gives a good indication of testicular damage, although normal levels do not rule out the possibility of azoospermia.

[Development of laryngeal papillomatosis in children. Apropos of 17 cases]. / Evolution de la papillomatose laryngée de l'enfant. A propos de 17 cas.

Seventeen children (ages ranging from 2 to 11 years at the onset of the study) were followed for 24.5 +/- 15 months (3 to 47 months) for a laryngeal papillomatosis requiring tracheotomy in 14. In 8 of the children evolution was low with a decrease or disappearance of relapses. On the contrary, 9 children, i.e. more than half the cases, presented with highly crippling disease, with frequent relapses of the laryngeal papillomas, extension of the lesions to the trachea, bronchi or even lungs, and local laryngeal complications (synechiae, sub-glottic stenosis). Medical anti-proliferative treatments had no effect. These children were submitted to iterative excisions. In 4 of them tracheotomy remained necessary after 3 years of evolution and their vital prognosis might become involved, either because of local complications or due to the extension of the lesions.

[Middle-term course of craniopharyngiomas in children as a function of initial therapeutic choice]. / Evolution à moyen terme des craniopharyngiomes de l'enfant en fonction des choix thérapeutiques initiaux.

Despite numerous studies and publications, the treatment of craniopharyngiomas in children remains controversial. The present series of 33 cases, followed for the last 10 years, is analysed according to therapeutic protocols jointly defined, case by case, from each patient's features and in restricting the extent of surgical excisions. In agreement with other recently published series, two options give superior results: complete excision, when the risk is low; in the other cases, partial excision or rather a simple biopsy or decompression, followed by irradiation. Risks of relapse are thus quite reduced and mortality greatly reduced. The unavoidable consequence of hypopituitarism is easily treated. However, the frequency of psychic and/or neurologic sequellae as well as the risk of post-radiation complications should not be disregarded when selecting treatment.

[Paraplegia complicating surgery for coarctation of the aorta]. / Paraplégie compliquant une intervention pour coarctation aortique.

A case of paraplegia occurring during surgery for coarctation of the aorta in a 28 month-old child is reported. Paraplegia was due to medullary ischemia, probably related to insufficient collateral circulation. Such ischemic accidents generally remain unforeseeable and no good prevention is available. This rare operative complication should not alter the present management of coarctation of the aorta.