Periosteal preservation: a new technique in resection of bone high-grade malignant tumors in children-about eleven cases.

OBJECTIVE: The purpose of this study was to describe a surgical technique of bone resection with periosteal preservation and reconstruction in patients with high-grade bone malignant tumors and to determine its effect on local recurrences, and time and quality of bone union in bone autografting reconstruction. PATIENTS AND METHODS: We retrospectively reviewed 11 cases of high-grade malignant bone tumors in children aged 4 to 16 years, who were treated with chemotherapy and tumor resection while preserving partially the adjacent periosteum. Tumors were located in the lower limb in eight cases; three tumors were in the humerus. The mean length of the bone defect after resection was 15.8 cm (range, 6-34.5 cm). Reconstruction was provided by non-vascularized autograft in eight cases (lower limb) and polymethyl methacrylate spacer in three cases (upper limb). Patients were followed up for a mean of 71 months. RESULTS: At the last follow-up, no patients had local recurrence. Three patients were dead because of metastasis. Bone union was good in time and quality in all children who had bone autografting. In cases of PMMA reconstruction, there was periosteal bone formation around the spacer. According to the MSTS functional score, patients with lower limb localizations had a mean score of 27.75 points and patients with upper limb localizations had a score of 24/30. CONCLUSION: Preservation of the periosteum in bone resection for malignant tumors could be a good adjuvant alternative for bone reconstruction, without increasing the risk of local recurrence. However, patients must be carefully selected.

Diagnosis of Constitutional Mismatch Repair-Deficiency Syndrome Based on Microsatellite Instability and Lymphocyte Tolerance to Methylating Agents.

BACKGROUND & AIMS: Patients with bi-allelic germline mutations in mismatch repair (MMR) genes (MLH1, MSH2, MSH6, or PMS2) develop a rare but severe variant of Lynch syndrome called constitutional MMR deficiency (CMMRD). This syndrome is characterized by early-onset colorectal cancers, lymphomas or leukemias, and brain tumors. There is no satisfactory method for diagnosis of CMMRD because screens for mutations in MMR genes are noninformative for 30% of patients. MMR-deficient cancer cells are resistant to genotoxic agents and have microsatellite instability (MSI), due to accumulation of errors in repetitive DNA sequences. We investigated whether these features could be used to identify patients with CMMRD. METHODS: We examined MSI by PCR analysis and tolerance to methylating or thiopurine agents (functional characteristics of MMR-deficient tumor cells) in lymphoblastoid cells (LCs) from 3 patients with CMMRD and 5 individuals with MMR-proficient LCs (controls). Using these assays, we defined experimental parameters that allowed discrimination of a series of 14 patients with CMMRD from 52 controls (training set). We then used the same parameters to assess 23 patients with clinical but not genetic features of CMMRD. RESULTS: In the training set, we identified parameters, based on MSI and LC tolerance to methylation, that detected patients with CMMRD vs controls with 100% sensitivity and 100% specificity. Among 23 patients suspected of having CMMRD, 6 had MSI and LC tolerance to methylation (CMMRD highly probable), 15 had neither MSI nor LC tolerance to methylation (unlikely to have CMMRD), and 2 were considered doubtful for CMMRD based on having only 1 of the 2 features. CONCLUSION: The presence of MSI and tolerance to methylation in LCs identified patients with CMMRD with 100% sensitivity and specificity. These features could be used in diagnosis of patients.

Prognostic factors in children with extracranial malignant germ cell tumors: a monocentric pediatric Tunisian study.

Background Extracranial Germ cell tumors (GCT) are a rare and a heterogeneous group of pediatric cancers but highly curable. Aim We aimed to review management, outcome and prognostic factors that influence overall survival (OS) in a pediatric Tunisian oncologic unit. Methods We retrospectively evaluated between January 1998 and December 2012, 33 patients affected by extracranial germ cell tumors and treated according to TGM95 protocol established by the SFOPin a pediatric Tunisian oncologic unit. Results Patients had a mean age of 57 months (ranges: 1 day-13 years). There were 19 girls and 14 boys. Primary sites included 12 sacrococcygeal, 11 ovarian, 6 testicular, 3retro peritoneal and 1 mediastinal site. After a mean follow up of 26.1 months (ranges: 0-96 months), OSat 2 years and 5 years were respectively 82% and 75%. Event-free survival were respectively 79% at 2 years and 74% at 5 years. Various prognostic factors have been studied according to Kaplan-Meier. Univariate analyses identified significant factors which influence strongly OS: the stage (p=0.04), the completeness of surgery (p<0.001) and the relapse (p = 0, 0001). A multivariate study showed that only the quality of resection and the clinical stage remained strong significant prognostic factors (p=0,021) for 5-year OS. Conclusion Disease stage, completeness of surgery and relapse have been established as the most powerful prognostic parameter in our analysis. The improvement of survival of patients affected by extracranial germ cell tumors in Tunisia is a real achievement mainly due to the success of salvage treatments.

Impact of Music Therapy on Quality of Life in Children with Cancer.

BACKGROUND: Music therapy (MT) is a non-pharmacological treatment increasingly used to reduce stress and anxiety in hospitalized children affected by cancers. The aim of this study was to evaluate the impact of MT on quality of life in children with cancer and determine its effect on cardiorespiratory rates. METHODS: We conducted a quasi-experimental study between 1 April and 31 August 2021 at Bechir Hamza children's Hospital in Tunis, including children treated for cancer. The child or parent completed the PedsQL Module Cancer French version 3.0 questionnaires before and after four weekly music therapy sessions. The child's respiratory and heart rates were measured before and after each session. RESULTS: We included 20 children whose mean age was 7 ± 4.5 years. The median value of the total questionnaire score increased from 57 [46; 70] to 72 [67; 85] (p < 10-3) noting a significant reduction in pain (p = 0.02), nausea (p = 0.009), and anxiety related to medical procedures (p = 0.009) and worry about the future (p = 0.005). We highlighted a significant decrease in respiratory and heart rate after MT (p < 0.05). CONCLUSIONS: MT has positive impact on quality of life in children with cancer and reduces stress by lowering their cardiorespiratory rates.

[Chemotherapy-induced febrile neutropenia in a Tunisian Department of Pediatric Oncology]. / Neutropénie fébrile chimio-induite dans une unité d'oncologie pédiatrique tunisienne.

Chemotherapy-induced neutropenia (FN) is the most common infectious complication in pediatric oncology. To our knowledge, no pediatric research has been published in Tunisia. The purpose of our study was to describe the features of FN among Tunisian children and to investigate factors correlated with FN. We conducted a prospective study of children with chemotherapy-induced FN at the Department of Pediatric Medicine A of the Tunis Children´s Hospital from July 2019 to December 2019. We recorded 50 episodes of FN in 32 patients whose mean age was 5.3 years (3 months-16 years). We included 26 patients with solid tumors (81%) and six patients with hemopathies (18.7%). The mean time between last treatment and fever onset was 10.67 days. Bacteriological investigation was contributory in 18% of cases and mainly showed gram positive cocci. Therapeutic protocol including 1st line empirical antibiotic therapy (3rd generation cephalosporin with aminoglycoside) was effective in 62% of cases. Mortality rate of patients with FN was 2%. The statistical study did not reveal any factor of correlation with late-onset neutropenia. In conclusion, our results are consistent with literature data on bacteriological documentation and mortality. Our 1st line treatment option based on 3rd generation cephalosporin associated with aminoglycoside was effective in 2/3 of the cases. In the future, oral antibiotics may be considered in patients at low risk for infection.

Scurvy still exists in children: A case report.

Scurvy is one of the oldest diseases known to mankind. Although rare lately, the clinical suspicion arises in front of a precarious situation or deficient nutrition and food restriction secondary to a psychiatric condition, even in patients with non-specific complaints. We report the observation of a 6 -year- old boy, followed for autism since the age of 3 years and who was admitted for limping, hemorrhagic syndrome, arthritis and weakness. The diagnosis of child abuse was initially suspected but clinical and radiological abnormalities seen were characteristic of scurvy. Vitamin C level was undetectable. The child had an unbalanced diet.A favorable outcome was rapidly obtained following supplementation. Scurvy is rare, but it should be mentioned among children with psychiatric disorders, presenting with musculoskeletal manifestations or hemorrhagic syndrome. It is essential to prevent it by systematic dietary supplementation of vitamin C in children with eating difficulties.

Case Report: FOXP3 Mutation in a Patient Presenting With ALPS.

ALPS and IPEX are two well-characterized inborn errors of immunity with immune dysregulation, considered as two master models of monogenic auto-immune diseases. Thus, with autoimmunity as their primary clinical manifestation, these two entities may show clinical overlap. Traditionally, immunological biomarkers are used to establish an accurate differential diagnosis. Herein, we describe a patient who presented with clinical features and biomarkers fulfilling the diagnostic criteria of ALPS. Severe apoptotic defect was also shown in the patient's cell lines and PHA-activated peripheral blood lymphocytes. Sanger sequencing of the FAS gene did not reveal any causal mutation. NGS screening revealed a novel deleterious variant located in the N terminal repressor domain of FOXP3 but no mutations in the FAS pathway-related genes. TEMRA cells (terminally differentiated effector memory cells re-expressing CD45RA) and PD1 expression were increased arguing in favor of T-cell exhaustion, which could be induced by unrestrained activation of T effector cells because of Treg deficiency. Moreover, defective FOXP3 observed in the patient could intrinsically induce increased proliferation and resistance to apoptosis in T effector cells. This observation expands the spectrum of FOXP3 deficiency and underscores the role of NGS in detecting mutations that induce overlapping phenotypes among inborn errors of immunity with immune dysregulation. In addition, these findings suggest a potential link between FOXP3 and FAS pathways.

Pediatric Noncerebral Thromboembolism: Etiological Assessment and Outcome.

OBJECTIVE: To report clinical presentation and etiologic investigation findings during pediatric noncerebral thromboembolism. METHODS: Retrospective study of cases of vascular non cerebral thromboses admitted in Medicine infantile A Department of the Children's Hospital of Tunis over 08 years. RESULTS: We confirmed 14 cases of non cerebral vascular thromboses. So that these accidents constitute 0,26 ‰ of the overall etiologies of hospitalizations in the Department. The mean age of our patients was 56±41 months [25 days-12 1/2 years]. The sex ratio was 1.8. The vascular incident was venous in 2/3 of cases. The clinical presentation was mainly painful swelling in four cases, abrupt dyspnea and hematemesis in three cases each and the incident was locally asymptomatic in four cases. Thromboses locations included deep vein thrombosis of limbs (n=6), vena cava thrombosis (n=1), portal thrombosis (n=4) and pulmonary embolism (n=3). The promoting factors identified were: tumors in seven cases, thrombophilias and catheterization in four cases each, trauma, surgery and Behçet disease in one case each. Eleven patients received anticoagulant treatment including unfractioned heparin in three cases and low molecular weight heparin in the other cases. No one died while four patients developed sequelae. CONCLUSION: Vascular thromboses are rare in children. They are mostly venous and diagnosed in ill children especially those having central venous catheters. Outcome of pediatric thromboembolism depends on efficient anticoagulation therapy which is well tolerated by children.