Le cancer en milieu chirurgical pédiatrique au Togo

Introduction: Le but de ce travail était de relever les aspects épidémiologiques des cancers de l'enfant en milieu chirurgical, décrire les problèmes posés par ces cancers et éval er les résultats de leur prise en charge Méthodes: Il s'agit d'une étude rétrospective analytique sur dossiers de patients âgés de moins de 15 ans pris en charge dans le service de chirurgie pédiatrique pour cancer solide de preuve anatomopathologique entre janvier 1987 et décembre 2010. Jusqu'en 2010, les hôpitaux publics du Togo ne disposaient pas d'imagerie par résonance magnétique ni de la tomodensitométrie. Il n'existe pas de service d'oncologie pédiatrique, ni de radiothérapie au Togo. Depuis quelques années maintenant, le Togo a intégré le Groupe Franco Africain d'oncologie Pédiatrique (GFAOP) et les patients bénéficient  gracieusement des antimitotiques pour la prise en charge de certains cancers. Résultats: Trente un  patients avaient été pris en charge dans le service de chirurgie pédiatrique pour cancer. Parmi eux, il y avait 18 garçons (58,06%) et 15 filles (41,94%). L'âge moyen des patients était de 7,62 ans (extrêmes: 3 mois et 15 ans). Les patients étaient également répartis dans les différentes tranches d'âge. Les  circonstances de découverte variaient selon le type de tumeurs. Les tumeurs des tissus mous  représentaient 51,61% des cas, les tumeurs germinales 25,81% des cas et les tumeurs osseuses 22,58% des cas. Le délai moyen d'évolution avant la consultation était de 4,6 mois (extrêmes : 2 et 14 mois). Le taux de décès était de 54,84% des cas. Conclusion: Les cancers solides de l'enfant sont  caractérisés par un retard à la consultation et un plateau à visée diagnostique et thérapeutique très limité entrainant de ce fait une forte mortalit

MG132 Induces Progerin Clearance and Improves Disease Phenotypes in HGPS-like Patients’ Cells

Progeroid syndromes (PS), including Hutchinson-Gilford Progeria Syndrome (HGPS), are premature and accelerated aging diseases, characterized by clinical features mimicking physiological aging. Most classical HGPS patients carry a de novo point mutation within exon 11 of the LMNA gene encoding A-type lamins. This mutation activates a cryptic splice site, leading to the production of a truncated prelamin A, called prelamin A ∆50 or progerin, that accumulates in HGPS cell nuclei and is a hallmark of the disease. Some patients with PS carry other LMNA mutations and are named “HGPS-like” patients. They produce progerin and/or other truncated prelamin A isoforms (∆35 and ∆90). We previously found that MG132, a proteasome inhibitor, induced progerin clearance in classical HGPS through autophagy activation and splicing regulation. Here, we show that MG132 induces aberrant prelamin A clearance and improves cellular phenotypes in HGPS-like patients’ cells other than those previously described in classical HGPS. These results provide preclinical proof of principle for the use of a promising class of molecules toward a potential therapy for children with HGPS-like or classical HGPS

Antisense-Based Progerin Downregulation in HGPS-Like Patients’ Cells

International audienceProgeroid laminopathies, including Hutchinson-Gilford Progeria Syndrome (HGPS, OMIM #176670), are premature and accelerated aging diseases caused by defects in nuclear A-type Lamins. Most HGPS patients carry a de novo point mutation within exon 11 of the LMNA gene encoding A-type Lamins. This mutation activates a cryptic splice site leading to the deletion of 50 amino acids at its carboxy-terminal domain, resulting in a truncated and permanently farnesylated Prelamin A called Prelamin A ∆50 or Progerin. Some patients carry other LMNA mutations affecting exon 11 splicing and are named " HGPS-like " patients. They also produce Progerin and/or other truncated Prelamin A isoforms (∆35 and ∆90) at the transcriptional and/or protein level. The results we present show that morpholino antisense oligonucleotides (AON) prevent pathogenic LMNA splicing, markedly reducing the accumulation of Progerin and/or other truncated Prelamin A isoforms (Prelamin A ∆35, Prelamin A ∆90) in HGPS-like patients' cells. Finally, a patient affected with Mandibuloacral Dysplasia type B (MAD-B, carrying a homozygous mutation in ZMPSTE24, encoding an enzyme involved in Prelamin A maturation, leading to accumulation of wild type farnesylated Prelamin A), was also included in this study. These results provide preclinical proof of principle for the use of a personalized antisense approach in HGPS-like and MAD-B patients, who may therefore be eligible for inclusion in a therapeutic trial based on this approach, together with classical HGPS patients

Management of acute sickle cell priapism in an African (Togo) pediatric department includes conservative measures and intracavernous epinephrine which is safe and efficacious

Abstract Priapism is a well‐known urologic complication of sickle cell anemia. This study describes the results of a protocol for the treatment of acute priapism by intracavernous injection of epinephrine due to unavailability of etilefrine. A descriptive cross‐sectional study of 18 cases of acute priapism in sickle cell patients treated in the pediatric department of the Sylvanus Olympio CHU from January 1 to December 31, 2020. The average age was 21.7 ± 7.7 years, the youngest patient was 8 and the oldest was 32 years old. Students represented 61.1% of the patients. The hemoglobin profiles were homozygous SS (n = 14) and double heterozygous SC (n = 4). Most of the crisis (83.3%) occurred at night. Most of the patients (66.7%) came to the hospital before the sixth hour of crisis, one patient came by the 48th hour. Walking was the most self‐relief method tried by patients (67%). It was followed by a cold penile bath, attempted urination, body bath, and lastly lukewarm bath. Fourteen patients had a history of chronic intermittent priapism. The average pain intensity was 9.5 ± 0.9 with restlessness (33.3%) and crying (33.3%). Fifteen patients were treated upon admission with an intracavernosal injection of epinephrine, and three patients were first drained. Thirteen patients achieved remission immediately, while five patients required a second injection and only one had to be drained before remission. Tolerance was good. One patient had a borderline systolic blood pressure. One erectile weakness case was noticed and no cases of sexual impotence. Epinephrine by intracavernosal injection is an efficient treatment for acute priapism in sickle cell patients. Epinephrine, which has a good tolerance in pediatric and young adult patients, should be used in lieu of etilefrine due to its unavailability in areas where it is unavailable