[Management of fetal growth restriction in France: Survey of teaching hospitals and tertiary referral centers]. / Prise en charge du retard de croissance intra-utérin en France : enquête auprès des centres hospitalo-universitaires et maternités de type III.

OBJECTIVES: French Guidelines on Fetal Growth Restriction (FGR) were published in December 2013. It seemed interesting to us to carry out an inventory on the management of FGR in teaching hospitals and tertiary referral centers MATERIAL AND METHODS: We carried out a retrospective survey on the academic year 2020/2021. All teaching hospitals and level III maternity in mainland France were contacted (67). The questionnaire focused on the growth curves used, the etiological assessment carried out, the rate and modalities of antenatal surveillance as well as the criteria indicating a birth. RESULTS: The response rate was 76%. The CFEF curves are used for screening in 78.4% of centers and in the event of FGR in 39.2% of them. The etiological assessment includes a referent ultrasound in 62.7% of cases and amniocentesis is offered in 74.5% of hospitals in case of severe and early FGR. All centers use umbilical Doppler for FGR. The fetal heart rate is monitored between once a week to three times a day in the event of cerebro-placental redistribution. In case of reverse flow, birth is induced from 28 weeks on for some teams while others continue the pregnancy until 39 weeks. In case of cessation of fetal growth, the expected terms of birth are between 28 and 38 weeks. CONCLUSION: There is great heterogeneity in the management of FGR, particularly in terms of antenatal surveillance and the term of birth envisaged.

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.

Is alpha-fetoprotein decline a prognostic factor of childhood non-seminomatous germ cell tumours? Results of the French TGM95 study.

PURPOSE: In adults' non-seminomatous germ cell tumours (NS-GCT), alpha-fetoprotein (AFP) decline was identified as an important prognostic factor. We investigated its prognostic value in the French TGM95 study for childhood NS-GCT. PATIENTS AND METHODS: Three risk groups were defined: low risk (LR: localised and completely resected pS1, AFP<15000 ng/ml), with a 'wait-and-see' strategy; intermediate-risk (IR: localised incompletely resected, AFP<15000 ng/ml) with 3-5 vinblastine-bleomycine-cisplatin courses; high risk (HiR: AFP≥15000 ng/ml and/or metastatic) with 4-6 etoposide-ifosfamide-cisplatin courses. The multivariable prognostic analysis for progression-free survival (PFS) included age (±10 years), primary tumour site (1-testis, 2-ovary, 3-extragonadal), extent of disease (1-pS1, 2-loco-regional dissemination, 3-metastasis) and AFP (±10,000 ng/ml). AFP decline prognostic value was investigated in IR + HiR groups using predicted time to normalisation (TTN), AFP change, and difference between observed and expected (based on AFP half-life) area under the curve (O-E AUC). RESULTS: From January 1995 to December 2005, 239 patients (median age = 3years, 60 LR, 65 IR, 114 HiR) were included. Main sites were testis (n = 66), ovary (n = 77) and sacrococcygeal (n = 57). Five-year PFS and OS were 85% (95% confidence interval [CI] = 80-89%) and 93% (89-95%), respectively. Age ≥ 10 years (hazard ratio [HR] = 4.6, 95% CI = 2.1-10.1, p = 0.0001) and extragonadal primary (HR = 6.3, 95% CI = 2.0-19.9, p = 0.005) were significant prognostic factors. In AFP decline analysis (n = 151, 17 events), TTN (p = 0.61) and AFP change (p = 0.10) were not prognostic, whereas we showed a significant effect of O-E AUC (HR = 2.1, 95% CI = 1.0-4.2, p = 0.05). CONCLUSION: Age ≥ 10 years and extragonadal tumours remain as poor prognostic factors. Contrary to adults, TTN is not reliable in paediatric NS-GCT. The prognostic value of O-E AUC should be investigated in larger studies.

Impact on obstetric outcome of third-trimester screening for small-for-gestational-age fetuses.

OBJECTIVES: To evaluate the performance of screening for small-for-gestational-age (SGA) fetuses by ultrasound biometry at 30-35 weeks' gestation, and to determine the impact of screening on obstetric and neonatal outcomes. METHODS: For this prospective cohort study, pregnant women were recruited from two French university maternity centers between 2003 and 2006. Performance measures of third-trimester biometry for the prediction of SGA, defined as estimated fetal weight < 10(th) centile, were analyzed. Obstetric outcomes and neonatal health status were compared, first, between SGA neonates diagnosed correctly at ultrasound examination (true positive (TP); n = 45) and SGA neonates that went undiagnosed (false negative (FN); n = 110) and, second, between non-SGA neonates identified as normal at ultrasound examination (true negative (TN); n = 1641) and non-SGA neonates diagnosed incorrectly as SGA (false positive (FP); n = 101). RESULTS: In the prediction of SGA, third-trimester ultrasound had a sensitivity of 29.0% (95% CI, 22.5-36.6%) and specificity of 94.2% (95% CI, 93.0-95.2%). Positive and negative predictive values were 30.8% (95% CI, 23.9-38.7%) and 93.7% (95% CI, 92.5-94.8%), respectively. One hundred and ten SGA neonates went undiagnosed at ultrasound. Compared to the TN neonates considered as of normal weight at ultrasound, planned preterm delivery (before 37 weeks) and elective Cesarean section for a fetal growth indication were 2.4 (P = 0.01) and 2.85 (P = 0.003) times more likely to occur, respectively, in the FP group of non-SGA neonates, diagnosed incorrectly as SGA during the antenatal period. There was no statistically significant difference in 5-min Apgar score < 7, cord blood pH at birth < 7.15 and need for neonatal resuscitation between the two subgroups (TN vs FP and TP vs FN). CONCLUSIONS: The performance of third-trimester ultrasound screening for SGA seems poor, as it misses the diagnosis of a large number of SGA neonates. The consequences of routine screening for SGA in a low-risk population may lead to unnecessary planned preterm deliveries and elective Cesarean sections in FP pregnancies, without improved neonatal outcome in the FN pregnancies.

[Management of severe or persistent postpartum hemorrhage after vaginal delivery]. / Prise en charge obstétricale en cas d'hémorragie du post-partum qui persiste malgré les mesures initiales ou qui est sévère d'emblée, après accouchement par voie basse.

INTRODUCTION: This chapter is an update of the 2004 recommendations for the management of persistent or severe postpartum hemorrhage (PPH) after natural childbirth. Severe PPH is defined by estimated blood loss greater than 1000mL (gradeC). Persistent bleeding within 15 to 30minutes after diagnosis and initial treatment (gradeC) or abundant immediately (professional consensus) should lead to a further management. MATERIALS AND METHODS: A systematic review of the literature concerning the management of persistent or severe PPH was conducted on Medline and Cochrane Database, with no specified time period. RESULTS AND DISCUSSION: The initial clinical evaluation is the same whatever initial severity. Each possible cause of bleeding must be evaluated: uterine vacuity must be checked and birth canal lesions must be researched and repaired (gradeC). Sulprostone is effective for the treatment of severe or persistent PPH (EL4) and its use is recommended for the management of PPH resistant to oxytocin administration (grade B). In the current state of the literature, there is no argument for replacing sulprostone in France by dinoprostone or prostaglandins F2α (professional consensus). If oxytocin has been administered, it is not recommended to use misoprostol (EL1) as adjuvant treatment because there is no evidence of benefit in this indication (grade A). Balloon intra-uterine tamponade appears to be an efficient mechanical treatment of uterine atony in case of failure of the initial management by sulprostone. Tamponade allows avoiding the need for further interventional radiology or surgery in most cases (EL4). Intra-uterine tamponade may be offered in case of failure of sulprostone and prior to surgical management or interventional radiology (professional consensus). Its use is left to the discretion of the practitioner. Tamponade should not delay the implementation of further invasive procedures.

Prognosis of malignant sacrococcygeal germ cell tumours according to their natural history and surgical management.

INTRODUCTION: Malignant sacrococcygeal (SC) germ cell tumours (GCT) may be diagnosed as primary pelvic tumour or malignant recurrence of foetal SC teratoma (FSCT) operated during the neonatal period. In order to evaluate the difference between these two populations, the authors report their experience with SC-GCT registered in the French TGM 95 protocol. POPULATION AND METHODS: The protocol comprised risk-adapted-chemotherapy (CT) followed by surgery. Standard risk (SR: localized tumour completely resected) had no adjuvant therapy. Intermediate-Risk (IR: localized tumour, incomplete or no initial surgery with αFP<15,000 ng/ml) received Vinblastine-Bleomycin-Cisplatin regimen; while High-Risk (HR: αFP > 15,000 ng/ml and/or metastases) received Etoposide-Ifosfamide-Cisplatin. RESULTS: Fifty-seven patients with SC-GCT, aged 0-80 months (median 16), were registered between 1995 and 2005. Nineteen patients had secondary SC-GCT after FSCT. All patients received CT: 17 IR and 1 SR after reevolution; 39 HR (25 with metastases). 51 patients underwent delayed surgery, which was incomplete in 8 patients. EVOLUTION: Seventy-two percent of the secondary SC-GCT had systematic biological follow-up. αFP increasing was the first presenting sign in 80% of the cases. Patients with secondary SC-GCT had a lower median αFP level at diagnosis, were less frequently classified as HR and received less CT. The two groups with secondary vs. primary SC-GCT had a statistically similar favourable outcome (Overall Survival: 93.8% vs. 86.2%; Event-Free Survival: 89.2 vs. 78.2%; p > 0.34 and >0.32), respectively, but with less burden of therapy. CONCLUSIONS: SC-GCT has a good overall prognosis provided complete surgery is achieved and CT is administered to IR and HR patients. SC-GCT in patients followed by αFP after treatment for FSCT had less tumour extension than newly-diagnosed patients, probably because of earlier detection of the disease.

Ovarian-sparing surgery for ovarian teratoma in children.

BACKGROUND: Ovarian teratoma (OT) is the most common ovarian neoplasm in children. Oophorectomy has been the standard treatment but may impair fertility. The aim of this study was to investigate the feasibility and outcome of ovarian-sparing surgery (OSS) for OT. PROCEDURE: We retrospectively studied all children treated for OT at a pediatric teaching hospital in Paris, France, between March 1992 and July 2006. OSS was performed when deemed technically feasible in patients who had no lymphadenopathy by preoperative imaging or surgical exploration, normal tumor marker levels, and calcifications on radiographs. RESULTS: We identified 30 patients, including 29 with unilateral OT and 1 with synchronous bilateral OT. Emergent surgery was performed in five patients, among whom four had ovarian torsion requiring oophorectomy and one underwent OSS. Of the 26 OTs in the 25 remaining patients, 10 were managed with OSS and 16 with oophorectomy. Subsequently, ultrasound monitoring detected OT development in the contralateral ovary in 4 (14%) patients, after a median of 3 years (range, 1-14 years); OSS was performed in all four cases. The patient with bilateral synchronous OT, managed by OSS initially, underwent unilateral oophorectomy 3 years later for a recurrence. Overall OSS was performed for 15 (42%) OTs. CONCLUSIONS: Our results suggest recommendations for preserving fertility whenever possible without compromising the oncological prognosis. In particular, OSS should be reserved for patients who meet all criteria for localized mature teratoma. Long-term follow-up is crucial.

[Malignant primary cardiac tumors in childhood and adolescence]. / Les tumeurs cardiaques primitives malignes de l'enfant et de l'adolescent.

Primary heart tumors are uncommon in children. The majority of them are benign, with only 10% malignant. Among malignant cardiac tumors, sarcoma (rhabdomyosarcoma, angiosarcoma, synovial sarcoma) and lymphoma (Burkitt's lymphoma, large B-cell lymphoma, lymphoblastic lymphoma) predominate. There are few published pediatric series on malignant primary cardiac tumors. We report here 3 observations of primary malignant cardiac tumors, 2 cases of sarcoma (angiosarcoma and synovial sarcoma) and 1 case of Burkitt's lymphoma. A precise pathological diagnosis is necessary for the proper management of these patients. For sarcoma, treatment associates surgery and chemotherapy. Surgery should be as complete as possible because of the lack of chemotherapy sensitivity of some sarcomas, mainly angiosarcoma and synovial sarcoma. Therefore, the prognosis of cardiac sarcoma remains poor. For primary cardiac lymphoma, management should not be different from lymphoma in other locations. Chemotherapy is the main treatment, and surgery has to be used only when complications occur. Prognosis depends on histology and not lymphoma location, and so is better than the prognosis for sarcoma.

[Juvenile granulosa-cell tumor: clinical and molecular expression]. / Tumeurs juvéniles de la granulosa: expression clinique et moléculaire.

Ovarian sex cord-stromal tumors are rare tumors that originate from the nongerminal cells of ovary. Two decades ago, the identification of juvenile granulosa-cell tumors (GCT), as a specific entity inside this group, allowed a better treatment of these tumors in children. However, little data have been reported on the natural course of the disease and reliable prognostic factors have not been yet defined. We here review the clinical and genetics aspects of granulosa tumors, based on a series of 40 children. This national collaborative study involved the French Society of Children Cancer and eight clinical departments of pediatric endocrinology. We found that early diagnosis of a tumor, revealed by clinical signs of hyperoestrogeny, is an important prognostic factor. The pathophysiology of these tumors is still debatable and several cellular- and molecular-abnormal signals could be implicated in their development. The role of growth factors and oncogenes through the signaling pathway of MAP kinase is still discussed. According to our data, FSH signaling-transduction pathway, such as a constitutionally activated Galphas, could also be implicated in the induction of granulosa cell proliferation and seems to modulate the invasiveness of the tumor. Last, we have described a low-expression pattern or an extinction of an ovarian-determination gene, FOXL2, which is related to a worse prognosis of this tumor.

Management of Wilms tumors in Drash and Frasier syndromes.

BACKGROUND: Children with WT1 gene-related disorders such as Denys-Drash syndrome (DDS) and Frasier syndrome (FS) are at increased risk of Wilms tumor and end-stage renal disease. We investigated whether Wilms tumors in these patients displayed a specific phenotype or behavior and whether nephron-sparing surgery was beneficial. PROCEDURE: We retrospectively studied all patients with DDS, FS, or other WT1 mutations treated at our institutions between 1980 and 2007. RESULTS: We identified 20 patients, of whom 18 had benign or malignant tumors. Wilms tumors occurred in 15 patients, being unilateral in 10 and bilateral in 5 (20 tumors). Median age at Wilms tumor diagnosis was 9 months. No patients had metastases. According to the International Society of Pediatric Oncology Working Classification, there were 19 intermediate-risk tumors and one high-risk tumor; no tumor was anaplastic. In patients with nephropathy who underwent unilateral nephrectomy for Wilms tumor or nephron-sparing surgery for bilateral Wilms tumor, mean time to dialysis was 11 or 9 months, respectively. Other tumors included three gonadoblastomas (in two patients), one retroperitoneal soft-tissue tumor, and one transitional cell papilloma of the bladder. Two patients, both with stage I Wilms tumor, died from end-stage renal disease-related complications. The median follow-up time for the 18 survivors was 136 months (range, 17-224 months). CONCLUSION: Most Wilms tumors in children with WT1-related disorders were early-stage and intermediate-risk tumors, with a young age at diagnosis. In patients without end-stage renal disease, nephron-sparing surgery should be considered for delaying the onset of renal failure.

Specific cytogenetic abnormalities are associated with a significantly inferior outcome in children and adolescents with mature B-cell non-Hodgkin's lymphoma: results of the FAB/LMB 96 international study.

Clinical studies showed that advanced stage, high LDH, poor response to reduction therapy and combined bone marrow and central nervous system disease are significantly associated with a decreased event-free survival (EFS) in pediatric mature B-cell non-Hodgkin's lymphoma (B-NHL) treated on FAB/LMB96. Although rearranged MYC/8q24 (R8q24) is characteristic of Burkitt lymphoma (BL), little information is available on other cytogenetic abnormalities and their prognostic importance. We performed an international review of 238 abnormal karyotypes in childhood mature B-NHL treated on FAB/LMB96: 76% BL, 8% Burkitt-like lymphoma, 13% diffuse large B-cell lymphoma (DLBCL). The main BL R8q24-associated chromosomal aberrations were +1q (29%), +7q and del(13q) (14% each). The DLBCL appeared heterogeneous and more complex. Incidence of R8q24 (34%) was higher than reported in adult DLBCL. The prognostic value of cytogenetic abnormalities on EFS was studied by Cox model controlling for the known risk factors: R8q24, +7q and del(13q) were independently associated with a significant inferior EFS (hazard ratio: 6.1 (P=0.030), 2.5 (P=0.015) and 4.0 (P=0.0003), respectively). The adverse prognosis of R8q24 was observed only in DLBCL, whereas del(13q) and +7q had a similar effect in DLBCL and BL. These results emphasize the significant biological heterogeneity and the development of cytogenetic risk-adapted therapy in childhood mature B-NHL.

[Pediatric non-Hodgkin's lymphoma: primary surgical management of patients presenting with abdominal symptoms. Recommendations of the Lymphoma Committee of the French Society to Combat Pediatric Cancers (SFCE)]. / Lymphome non-Hodgkinien de l'enfant: prise en charge chirurgicale lors d'un tableau abdominal révélateur.

Over the past two decades, dramatic improvements in the treatment of children with Non-Hodgkin's Lymphoma have led to cure rates close to 90%, even in advanced-stage disease. The most frequent localization is abdominal, where Burkitt or Burkitt-like subtypes are predominant. Initial management often occurs in the setting of a urgent surgical intervention where multiple complications may gravely threaten prognosis within days or even hours. The SFCE Lymphoma Committee's guidelines for optimal management include: 1) The diagnosis of lymphoma should be systematically evoked whenever the clinical context is not consistent with idiopathic intussusception, particularly in children over the age of 3 or when clinical and/or ultrasound findings are not typical; 2) Limited bowel resection should be performed only if it allows complete tumor removal and is technically simple without extensive dissection or risk of major complications; 3) If surgical resection is likely to be difficult, risky, or incomplete, surgery should be limited to sampling of peritoneal fluid and tumor; 4) In all cases, adequate tissue should be obtained and sent to the pathology department in appropriate media Analysis of tumor material may require, in addition to histology and cytology, immunophenotyping, cytogenetics, and molecular biology studies in order to arrive at an accurate diagnosis and prognosis and to guide treatment choices.

[Not Available]. / Lymphome non-Hodgkinien de l'enfant : prise en charge chirurgicale lors d'un tableau abdominal révélateur: Recommandations du « Comité lymphome ¼ de la Société française de lutte contre les cancers de l'enfant et de l'adolescent (SFCE).

A. Delarue, C. Bergeron, F. Mechinaud-Lacroix, C. Coze, M. Raphael, C. Patte, pour le « Comité Lymphome ¼ de la SFCE Over the past two decades, dramatic improvements in the treatment of children with Non-Hodgkin's Lymphoma have led to cure rates close to 90%, even in advanced-stage disease. The most frequent localization is abdominal, where Burkitt or Burkitt-like subtypes are predominant. Initial management often occurs in the setting of a urgent surgical intervention where multiple complications may gravely threaten prognosis within days or even hours. The SFCE Lymphoma Committee's guidelines for optimal management include: 1) The diagnosis of lymphoma should be systematically evoked whenever the clinical context is not consistent with idiopathic intussusception, particularly in children over the age of 3 or when clinical and/or ultrasound findings are not typical; 2) Limited bowel resection should be performed only if it allows complete tumor removal and is technically simple without extensive dissection or risk of major complications; 3) If surgical resection is likely to be difficult, risky, or incomplete, surgery should be limited to sampling of peritoneal fluid and tumor; 4) In all cases, adequate tissue should be obtained and sent to the pathology department in appropriate media Analysis of tumor material may require, in addition to histology and cytology, immunophenotyping, cytogenetics, and molecular biology studies in order to arrive at an accurate diagnosis and prognosis and to guide treatment choices.

[Treatment of childhood cancer in Africa. Action of the Franco-African childhood cancer group]. / Le traitement des cancers de l'enfant en Afrique. Travaux du groupe franco-africain d'oncologie pédiatrique.

The childhood cancer survival rate is currently 75% in industrialized countries. Rates in developing countries are much lower. The Franco-African Childhood Cancer Group (French acronym, GFAOP) was founded in 2000 with aim of reducing this unfavorable situation in Africa. The GFAOP has developed two forms of action. The main form consists of organizing two- to twelve-month training sessions for physicians and nurses in France and Morocco. The other form involves assessing the feasibility of modern treatment protocols for various cancers in Africa. The first feasibility trials were carried out on nephroblastoma and Burkitt's lymphoma in 12 pilot units in North Africa, West Africa, and Madagascar. In the first study from 2001 to 2005 we treated 306 cases of Burkitt's lymphoma using French LMB protocols adapted to the African setting and achieved a survival rate of 61%. A second study started in 2005 using Endoxan alone achieved a highly satisfactory survival rate of 73% for neuroblastoma in all stages except bilateral. Altogether from 2001 to 2007 more than 1000 cases of nephroblastoma and Burkitt's lymphoma were treated in African hospitals by African doctors and nurses. No patients were transferred to Europe. The GFAOP supplied drugs when necessary and took care of most travel expenses. African and French doctors worked together on protocol design, trial management, and data analysis. These promising results show that the latest therapeutic techniques can be used to treat childhood cancer in Africa by adapting the protocol to conditions in developing countries. Sanofi-Aventis Laboratories in association with the International Union against Cancer has launched a major campaign to improve Pediatric Oncology in developing countries. Projects in four GFAOP units are being financed through this campaign. In 2006 the GFAOP began assessment of two new treatment protocols, i.e., one for acute lymphoblastic leukemia and the other for Hodgkin's disease. Two other projects are being planned, i.e., one for treatment of retinoblastoma and the other for treatment of some types of brain tumors.

Dactinomycin-induced, severe lichenoid eruption in a child.

There is little information in the medical literature about skin rashes associated with dactinomycin in the absence of radiotherapy. We report a 12-month-old male child who developed a severe cutaneous reaction that consisted of a widespread pruritic papular eruption associated with fever and a poor general state after dactinomycin administration. Skin biopsy specimen findings confirmed the diagnosis of lichenoid eruption. The rash improved with topical steroid treatment and completely resolved within 1 month with persistence of a residual mild hyperpigmentation. Dactinomycin administration was discontinued for the remaining cycles of chemotherapy.