Central nervous system relapse in high-risk stage 4 neuroblastoma: The HR-NBL1/SIOPEN trial experience.

BACKGROUND: There is rising concern on the impact of new strategies, such as high-dose chemotherapy (HDC) and immunotherapy, on the pattern of relapse in high-risk neuroblastoma (HR-NBL). Our aim is to evaluate the incidence and identify risk factors for first recurrence in the central nervous system (CNS) in HR-NBL. PATIENTS AND METHODS: Data from patients with stage 4V HR-NBL included from February 2002 to June 2015 in the prospective HR-NBL trial of the European International Society of Pediatric Oncology Neuroblastoma Group were analysed. Characteristics at diagnosis, treatment and the pattern of first relapse were studied. CNS imaging at relapse was centrally reviewed. RESULTS: The 1977 included patients had a median age of 3 years (1 day-20 years); 1163 were boys. Among the 1161 first relapses, 53 were in the CNS, with an overall incidence of 2.7%, representing 6.2% of all metastatic relapses. One- and three-year post-relapse overall survival was 25 ± 6% and 8 ± 4%, respectively. Higher risk of CNS recurrence was associated with female sex (hazard ratio [HR] = 2.0 [95% confidence interval {CI}: 1.1-3.5]; P = 0.016), MYCN-amplification (HR = 2.4 [95% CI: 1.2-4.4]; P = 0.008), liver (HR = 2.5 [95% CI: 1.2-5.1]; P = 0.01) or >1 metastatic compartment involvement (HR = 7.1 [95% CI: 1.0-48.4]; P = 0.047) at diagnosis. Neither HDC nor immunotherapy was associated with higher risk of CNS recurrence. Stable incidence of CNS relapse was reported over time. CONCLUSIONS: The risk of CNS recurrence is linked to both patient and disease characteristics, with neither impact of HDC nor immunotherapy. These findings support the current treatment strategy and do not justify a CNS prophylactic treatment.

[Splenectomy in hemolitic disorders. Influence of Gilbert's disease in the occurrence of biliary complications]. / Esplenectomía en enfermedades hemolíticas. Influencia de la enfermedad de Gilbert en la aparición de complicaciones biliares.

INTRODUCTION: In patients with hemolytic disorders (HD) splenectomy is recommended between 6-12 years. A higher risk of biliary complications (BC) has been described in those with associated Gilbert's disease (GD), but the ideal surgical age has not been stablished yet. Our aim is to quantify the risk of BC in patients with HD and GD to assess the benefit of early splenectomy. MATERIAL AND METHODS: Retrospective study of splenectomies performed in patients with HD between 2000-2017. The incidence of BC, its clinical consequences (admission or invasive treatment) and time of onset were analyzed. Two groups were considered: patients with GD and without GD. Survival curves were obtained and compared with log-rank test. RESULTS: Fourty-four patients underwent splenectomy, 15 of them (34.1%) with HD+GD. The median age at surgery was 10.3 years (range 5.4-14.8). Twenty-nine (65.9%) had BC. Half of the patients with GD had BC before 8 years vs. 10,5 years in the cases without GD (log-rank 3.9, p= 0.05). Patients with GD had more BC (86.7% vs. 55.2%; Chi2= 4.37, p= 0.037). In the HD+GD group, 8 cases (53%) required admission vs.8 patients (31%) in the group HD without GD (Chi2= 2, p= 0.1). Invasive treatment was performed in 2 patients (13%) in the HD+GD group and 2 others (7.6%) in the group HD without GD (Chi2= 0.3, p= 0.6). CONCLUSIONS: In our series, the BC incidence was higher in patients with HD and GD. There was a trend towards an earlier presentation of BC in this group, but neither this data nor its clinical consequences allow us to recommend early splenectomy.

INTRODUCCION: En pacientes con enfermedades hemolíticas (EH) se recomienda esplenectomía entre 6-12 años. En aquellos con enfermedad de Gilbert (EG) asociada se ha descrito mayor riesgo de complicaciones biliares (CB), sin establecerse edad quirúrgica óptima. Nuestro objetivo es cuantificar el riesgo de CB en pacientes con EH y EG para valorar el beneficio de esplenectomía temprana. MATERIAL Y METODOS: Estudio retrospectivo de las esplenectomías realizadas en pacientes con EH entre 2000-2017. Se analizó la incidencia de CB, su repercusión clínica (ingreso o tratamiento invasivo) y momento de aparición. Se consideraron dos grupos: pacientes con EG y sin EG. Se obtuvieron curvas de supervivencia y se compararon mediante log-rank test. RESULTADOS: Se realizaron 44 esplenectomías, 15 de ellas (34,1%) en pacientes con EH+EG. La edad mediana en la cirugía fue 10,3 años (rango 5,4-14,8). Veintinueve (65,9%) presentaron CB. El 50% de los pacientes con EG las presentaron antes de los 8 años vs.10,5 años en los casos sin EG (log-rank 3,9; p= 0,05). Los pacientes con EG presentaron más CB (86,7% vs. 55,2%; Chi2= 4,37, p= 0,037). En el grupo EH+EG, 8 casos (53%) necesitaron ingreso vs. 8 (31%) en el grupo sin EG (Chi2= 2, p= 0,1). El tratamiento invasivo fue necesario en 2 pacientes (13%) del grupo EH+EG y 2 pacientes (7,6%) del grupo sin EG (Chi2= 0,3, p= 0,6). CONCLUSIONES: En nuestra serie, la incidencia de CB fue superior en los pacientes con EG. Existió una tendencia a la presentación más temprana de CB en este grupo, pero ni este dato ni su repercusión clínica nos permiten recomendar la esplenectomía temprana.

Could other viruses cause pediatric posttransplant lymphoproliferative disorder?

INTRODUCTION: Posttransplant lymphoproliferative disorder (PTLD) constitutes a heterogeneous group of diseases. We summarize the experience of our hospital, one of Spain's largest series of renal (294), liver (47) and allogeneic stem cell transplants (67), where four cases of PTLD have developed related to complex viral infections. METHODS: Case 1 was a 24-month-old boy diagnosed with acute lymphoblastic leukemia who underwent allogeneic stem-cell transplantation (SCT). He was seropositive for Epstein-Barr virus (EBV) and developed an aggressive Bcell non-Hodgkin's lymphoma (B-NHL) related to EBV reactivation and human herpesvirus 6 (HHV-6) infection. Cases 2, 3, and 4 developed after kidney transplantation and were all EBV seronegative. Case 2 had associated cytomegalovirus (CMV) and EBV infection. Cases 3 and 4 only revealed EBV viral load. Cases 1, 3, and 4 progressed rapidly, with fatal outcome. Global incidence of PTLD in our series is 1.1%. CONCLUSION: PTLD is a rare but life-threatening condition. Although EBV plays a clear role in its pathogenesis, other associated viral infections could trigger this situation. Current therapies include rituximab, decreasing immunosuppressive drugs. and conventional chemotherapy.

[Intratesticular calcifications in childhood]. / Calcificaciones intratesticulares en la edad pediátrica.

INTRODUCTION: Testicular microlithiasis (TM) represents an uncommon occurrence at paediatrics with a radiological incidence between 0.16 to 0.6% according to reports. The greater use of ultrasound as well as the availability of high-frequency probes has increased the number of incidental TM being diagnosed. MATERIAL AND METHOD: From January 1998 to October 2002 seven children, aged 9 to 13 years (average 11 years and 1 months), were diagnosed of MT in our department. Sonographic appearance was hyperechogenic multiple small foci of 1-3 mm without acoustic shadowing of the testicular parenchyma. AIM: To evaluate sonographic patterns of TM, their associations, clinical consequences and to determine their management. RESULTS: All children were asymptomatic and the reasons for the ultrasound were: cryptorchism (3), short height (1), gynecomastia (1), varicocele (1) and scrotum trauma (1). It should be noted that 3 of the cases showed bilateral TM. Out of 10 testicles with TM, 8 met classic testicular microlithiasis (CTM) criteria (at least one image that showed five or more microliths in either or both testes) and 2 had limited testicular microlithiasis (LTM) (to have at least one microlith). Clinical and radiological follow-up is being performed annually, ranging from 18 months to 6 years, during which there hasn't been progression or regression in the number of TM or in their distribution. In none of these cases there has been shown a related testicular cancer. CONCLUSIONS: In other broad reviews it has been shown that there is no evidence to suggest that the TM have to be considered as premalignant lesions by themselves. However, the association among TM and cancer exists. Because of that, and due to the lack of consensus, we recommend annual clinical and radiological (ultrasound) follow-up until puberty, and thereafter the patient should be informed of unknown natural history of this condition. We do not recommend more invasive procedures such as biopsy except: 1) apart form the TM there is a change in the echogenicity or 2) if there is a change in the number or distribution of the TM.

[Ultrasound role in assessment of vesicoureteral reflux endoscopic treatment results]. / Papel de la ecografía en la valoración del resultado del tratamiento endoscópico del RVU.

INTRODUCTION: Since the beginning of the application of the RVU treatment, the use of the ultrasound was used taking into account two main indications/symptoms: a) identification of the complications; b) assessment of the result (visualization of the implanted material and the presence of the "uretheral jet" by means or through/of ecodoppler-color). OBJECTIVE: To determine the value of the ultrasound in the assessment of the result of the endoscopic treatment of the RVU and in the detection of its complications. MATERIAL AND METHOD: From 2001-2002 we have carried out the endoscopic treatment to an overall of 261 ureteral units of all degree and etiology. 246 were assessed post-operation with an ultrasound per month and all of them were evaluated with a cistography after 3 months. In a random sample of 92 units, the result of the isotopic cistography has been compared with the visualization of the implanted material in the bladder; and in a random sample of 56 units, the result of the isotopic cistography has been compared with the presence of ureteral jet in the study with ecodoppler-color after moisturizing of the patient. In order to do, we have done two corresponding comparative charts 2 x 2 and we have calculated the Sensibility and Specificity of the tests, as well as their predictive positive and negative values, the degree of similarity of both tests with the Kappa index, and the degree of statistical relevance with Chi squared. RESULTS: The ultrasound did not show significant changes if compared to previous studies in 213 units (86,58 %) although in 5 patients an ectasia has been identified as attributed to the treatment. 3 of this patients have developed renoureteral pain, and in 2 pain has spontaneously disappeared as shown in later tests. The S and the E of the presence of implanted material is 94% and 10%respectively and its VPP and VPN of 80% and 10% and estadistical. The S and E of the jet visualization is 82% and 30%, with a VPP of 84% and a VPN of 27%, a level of statistical relevance of 0.836 and a degree of correlation of 0.121. CONCLUSIONS: Ultrasound is not a useful technique in the assessment of the result of the endoscopic treatment of the RVU. The role it plays in the assessment of complications is a small one and its use is only indicated to confirm the suspicion of ectasia in those patients that present renoureteral pain.

[Vesicoureteric reflux endoscopic treatment complications in childhood]. / Complicaciones del tratamiento endoscópico del reflujo vesicoureteral en la infancia.

INTRODUCTION: Nowadays, around 1% of children suffer from vesicoureteral reflux (VUR), which represents a risk factor for long-term kidney damage. In the last decade, development in this field has shown that subureteric endoscopic injection of bulking agents for childhood VUR is an acceptable alternative unlike long-term antibiotic prophylaxis and open surgery. OBJECTIVE: To establish the complications of childhood VUR endoscopic treatment. MATERIAL AND METHODS: A retrospective analysis was carried out for every patient treated endoscopically in our department from January 1999 to September 2003, with a total amount of 516 implants of submucous bulking agents. All patients were assessed with an ultrasound as a first diagnostic technique so as to establish the complications associated with it, especially ureteral obstruction and injected agent migration. RESULTS: Out of 516 cases, Macroplastique was used in 455, Deflux in 44 and Polytef in 17. 10 patients (1.9%) (5 girls/ 5 boys), with ages ranging from 15 months to 11,4 years, presented some kind of complications (Macroplastique was used in 8cases and Deflux in 2). Among them, 5 were remarkable due to an ureterohydronefrosis, 2 of which needed a nephrostomy. 3 patients presented an implant migration, 1 epididymitis and 1 bladder edema. CONCLUSIONS: Endoscopic bulking agent injection has become a safe alternative to open surgery in childhood VUR management.

Congenital intrahepatic portocaval shunt associated with trimethylaminuria

A case of congenital portal-systemic shunting due to an intrahepatic connection diagnosed by ultrasound scanning and color Doppler in an 8-month-old girl is reported. She began to manifest trimethylaminuria 3 years later. At 7 years of age, she is asymptomatic without therapeutic measures except for diet. This is the seventh reported case and the third in a child to our knowledge.

Congenital intrahepatic portocaval shunt associated with trimethylaminuria.

A case of congenital portal-systemic shunting due to an intrahepatic connection diagnosed by ultrasound scanning and color Doppler in an 8-month-old girl is reported. She began to manifest trimethylaminuria 3 years later. At 7 years of age, she is asymptomatic without therapeutic measures except for diet. This is the seventh reported case and the third in a child to our knowledge.