Fallo ovárico prematuro en supervivientes a un tumor sólido: puntos clave de manejo / Primary ovarian insufficiency in cancer survivors: Keys to optimal management

Introducción: La insuficiencia ovárica prematura (POI) conlleva importante morbilidad, causando infertilidad, disfunción sexual, disminución de la densidad ósea, riesgo cardiovascular, alteraciones emocionales y mortalidad precoz. Objetivo: Conocer la incidencia y el manejo actual de la POI en supervivientes a un tumor sólido en la infancia y/o adolescencia en nuestro medio. Material y métodos: Estudio observacional multicéntrico. Mujeres entre 12 y 18 años con diagnóstico de tumor sólido y criterios clínicos y/o analíticos de POI. El riesgo se estima según los criterios «The Pediatric Initiative Network of the Oncofertility Consortium». Resultados: Incidencia de 1,5 (30 casos de POI). Edad media 14±2,09. Los tumores sólidos que más se asociaron a la POI fueron: sarcoma de Ewing, tumores cerebrales y germinales. El 83% de los casos no realizó preservación previa al tratamiento. Un 63% no referían menarquia al diagnóstico de la POI. El 97% cumplían criterios de alto riesgo de toxicidad gonadal, a pesar de ello el 47% no realizó ninguna vigilancia previa al diagnóstico. La mediana de tiempo tras el diagnóstico y la aparición del evento es de 43,5 y 29,5 meses tras finalizar tratamiento. Las curvas de Kaplan-Meier, muestran que al 30% de los casos, aparecen en los 2 años tras el diagnóstico y las mujeres con estadio puberal 1 desarrollan insuficiencia más tardíamente que aquellas con estadio 5. Conclusiones: El seguimiento de mujeres en riesgo de la POI, es susceptible de mejora. Las herramientas actuales facilitan conocer el riesgo al planificar los tratamientos del tumor y realizar vigilancia, educación, diagnóstico precoz, preservación e instauración de tratamiento sustitutivo. Todo ello, supondría importantes mejoras en salud.(AU)

Introduction: Primary ovarian insufficiency (POI) carries significant morbidity, causing infertility, sexual disfunction, decreased bone density, cardiovascular risk, emotional distress and early mortality. Objective: To know the incidence and current management of POI in childhood/adolescent solid tumour survivors. Material and methods: We conducted a multicentre observational study. It included female patients aged 12 to 18 years with a diagnosis of solid tumour and meeting clinical or biochemical criteria for POI. The risk was estimated based on the criteria of the Pediatric Initiative Network of the Oncofertility Consortium. Results: We found an incidence of 1.5 (30 cases of POI): The median age at the time of the event was 14 years (standard deviation, 2.09). The solid tumours associated most frequently with POI were Ewing sarcoma and brain and germ cell tumours. Eighty-three percent of patients did not undergo fertility preservation. Sixty-three percent reported not having undergone menarche at the time of ovarian failure. Ninety-seven percent were at high risk of gonadal toxicity, yet 47% were not monitored before the diagnosis. The median time elapsed to the occurrence of the event was 43.5 months after diagnosis and 29.5 months after completing treatment. The Kaplan-Meier curves showed that approximately 30% of POI cases developed within 2 years of diagnosis and that women at Tanner stage 1 developed insufficiency later than women at Tanner stage 5. Conclusions: There is room for improvement in the followup of women at risk of POI in Spain. The tools currently available facilitate risk assessment at the time of treatment planning and allow the implementation of monitoring, education, early diagnosis, fertility preservation, and replacement therapy as needed. All of this would achieve significant improvement in health outcomes.(AU)

Primary ovarian insufficiency in cancer survivors: Keys to optimal management.

INTRODUCTION: Primary ovarian insufficiency (POI) carries significant morbidity, causing infertility, sexual disfunction, decreased bone density, cardiovascular risk, emotional distress and early mortality. OBJECTIVE: To know the incidence and current management of POI in childhood/adolescent solid tumour survivors. MATERIAL AND METHODS: We conducted a multicentre observational study. It included female patients aged 12-18 years with a diagnosis of solid tumour and meeting clinical or biochemical criteria for POI. The risk was estimated based on the criteria of the Pediatric Initiative Network of the Oncofertility Consortium. RESULTS: We found an incidence of 1.5 (30 cases of POI): The median age at the time of the event was 14 years (standard deviation, 2.09). The solid tumours associated most frequently with POI were Ewing sarcoma and brain and germ cell tumours. Eighty-three percent of patients did not undergo fertility preservation. Sixty-three percent reported not having undergone menarche at the time of ovarian failure. Ninety-seven percent were at high risk of gonadal toxicity, yet 47% were not monitored before the diagnosis. The median time elapsed to the occurrence of the event was 43.5 months after diagnosis and 29.5 months after completing treatment. The Kaplan-Meier curves showed that approximately 30% of POI cases developed within 2 years of diagnosis and that women at Tanner stage 1 developed insufficiency later than women at Tanner stage 5. CONCLUSIONS: There is room for improvement in the follow-up of women at risk of POI in Spain. The tools currently available facilitate risk assessment at the time of treatment planning and allow the implementation of monitoring, education, early diagnosis, fertility preservation, and replacement therapy as needed. All of this would achieve significant improvement in health outcomes.

Identification of germline cancer predisposition variants in pediatric sarcoma patients from somatic tumor testing.

Genetic predisposition is an important risk factor for cancer in children and adolescents but detailed associations of individual genetic mutations to childhood cancer are still under intense investigation. Among pediatric cancers, sarcomas can arise in the setting of cancer predisposition syndromes. The association of sarcomas with these syndromes is often missed, due to the rarity and heterogeneity of sarcomas and the limited search of cancer genetic syndromes. This study included 43 pediatric and young adult patients with different sarcoma subtypes. Tumor profiling was undertaken using the Oncomine Childhood Cancer Research Assay (Thermo Fisher Scientific). Sequencing results were reviewed for potential germline alterations in clinically relevant genes associated with cancer predisposition syndromes. Jongmans´ criteria were taken into consideration for the patient selection. Fifteen patients were selected as having potential pathogenic germline variants due to tumor sequencing that identified variants in the following genes: CDKN2A, NF1, NF2, RB1, SMARCA4, SMARCB1 and TP53. The variants found in NF1 and CDKN2A in two different patients were detected in the germline, confirming the diagnosis of a cancer predisposition syndrome. We have shown that the results of somatic testing can be used to identify those at risk of an underlying cancer predisposition syndrome.

Clinical management of the acute complications of sickle cell anemia: 11 years of experience in a tertiary hospital.

INTRODUCTION: Sickle cell disease is an emerging anemia in Europe leading to high morbidity with severe acute complications requiring hospital admission and chronic consequences. The management of these patients is complex and needs interdisciplinary care. The objective is to analyze clinical characteristics and management of patients with sickle cell disease admitted for acute complications. METHODS: Retrospective descriptive study of admissions for acute complications of patients with sickle cell disease under 16 years of age in a tertiary hospital between 2010 and 2020. Clinical, laboratory and radiological data were reviewed. RESULTS: We included 71 admissions corresponding to 25 patients, 40% diagnosed by neonatal screening. Admissions increased during this period. The most frequent diagnoses were vaso-occlusive crisis (35.2%), febrile syndrome (33.8%) and acute chest syndrome (32.3%). Nine patients required critical care at PICU. Positive microbiological results were confirmed in 20 cases, bacterial in 60%. Antibiotic therapy was administered in 86% of cases and the vaccination schedule of asplenia was adequately fulfilled by 89%. Opioid analgesia was required in 28%. Chronic therapy with hydroxyurea prior to admission was used in 41%. CONCLUSIONS: Acute complications requiring hospital admission are frequent in patients with sickle cell disease, being vaso-occlusive crisis and febrile syndrome the most common. These patients need a high use of antibiotics and opioid analgesia. Prior diagnosis facilitates the recognition of life-threatening complications such as acute chest syndrome and splenic sequestration. Despite the prophylactic and therapeutic measures currently provided to these patients, many patients suffer acute complications that require hospital management.

Pediatric Intentional Self-poisoning Evaluated in the Emergency Department: An International Study.

BACKGROUND: Suicide is a growing public health problem during late childhood and adolescence. The leading method of suicide attempts in this age group is intentional self-poisoning. A first self-poisoning episode is a strong predictor of subsequent suicide and premature death. The objective of this study was to analyze the presentation and management of children younger than 18 years with intentional self-poisonings admitted to an emergency department (ED) in a global research network of pediatric EDs. METHODS: We performed a secondary analysis of a large, international, multicenter, cross-sectional prospective registry of childhood poisoning presentations to 105 EDs in the Pediatric Emergency Research Networks (PERN) network. Data collection started at each ED between January and September 2013 and continued for 1 year. RESULTS: During the study period, we included 1688 poisoning exposures. Of these, 233 (13.8%) were intentional self-poisonings, with significant variation between regions. Female/male ratio was 4.7/1 and most occurred at home. The most common toxicants were therapeutic drugs, mainly psychotropics and analgesics. Ninety patients (38.6%) gave a history of a previous episode of intentional self-poisoning. Sixty-three children (27.0%) were not assessed by a psychiatric service nor transferred to a psychiatric inpatient facility. No patient died. There was significant variation in the involved toxicants and interventions among EDs in different global regions. CONCLUSIONS: Most intentional self-poisoning presentations to pediatric EDs globally are related to intentional ingestions of therapeutic drugs at home by females. Best practices have to be translated into care to guarantee the best outcomes of these patients.