Gonadal function and fertility in males survivors treated for Hodgkin's disease in Iran

Objectives: To investigate the effect of chemotherapy on gonadal function of young men cured of childhood Hodgkin's disease. Methods: Young adult males surviving Hodgkin's disease, aged 17 and over at least 2 years after therapy were studied in Ali Asghar Children's Hospital, Tehran, Iran from March 2000 to March 2005. Clinical evaluation for secondary sexual characteristics, semen analysis, follicle stimulating hormone (FSH), luteinizing hormone (LH), and testosterone was studied in 33 survivors of Hodgkin's disease. Results: The age at diagnosis was 5-15 years, median 9 years, age at study 17-29 years, median 19 years old. The median duration off therapy was 7 years (2-20 years). All 33 patients received chemotherapy as follows: 32 patients received nitrogen mustard (mechlorethamine), vincristine (Oncovin), procarbazine, prednisone (MOPP)/doxorubicin (adriamycin), bleomycin, vinblastine, dacarbazine (ABVD) 6-8 cycles, 5 of whom after relapses received other protocols. One received only MOPP. Twenty-seven (81.8) had azoospermia, 2 had severe oligospermia, 3 had oligospermia, and one had normal sperm count (58000,000). All patients had normal secondary sexual characteristic. The FSH, and LH in 6/33 patients were above normal. Testosterone in 3/33 was below normal. Conclusion: A prepubertal status does not protect the gonads from the harmful effect of chemotherapy, and approximately 87 of male survivors of Hodgkin's disease develop azoospermia or severe oligospermia

Aggressive intra-abdominal fibromatosis in children and response to chemotherapy

Intra-abdominal fibromatosis (IAF) is a rare benign neoplasm arising from the abdominal fibrous tissue, mostly in the mesentery. IAF is characterized by a tendency to infiltrate the surrounding vessels and vital structures and recurrence after usually incomplete surgical removal. Accordingly, IAF is associated with considerable morbidity and mortality. The authors report on a boy who presented with a large IAF at the age of 5 years. Within 6 months after initial presentation, he underwent 4 subsequent abdominal explorations for diagnosis, tumor reduction, and intestinal obstructions. IAF was confirmed by the presence of vimentin and absence of other biological cell markers. Due to accelerated tumor growth and deteriorated general condition, as a last resort, a chemotherapy trial with vincristin and methotrexate was carried out. This regimen proved to be effective in reducing the tumor burden and improving the patient's general condition. Outcome of IAF depends on early diagnosis and complete tumor resection, and, if indicated, timely employment of neo/adjuvant chemotherapy. Radiotherapy must be considered in life-threatening conditions as the last resort in a growing child 2-4. Copyright © Taylor and Francis Inc

Plasticity of the human visual system after retinal gene therapy in patients with Leber's congenital amaurosis.

Much of our knowledge of the mechanisms underlying plasticity in the visual cortex in response to visual impairment, vision restoration, and environmental interactions comes from animal studies. We evaluated human brain plasticity in a group of patients with Leber's congenital amaurosis (LCA), who regained vision through gene therapy. Using non-invasive multimodal neuroimaging methods, we demonstrated that reversing blindness with gene therapy promoted long-term structural plasticity in the visual pathways emanating from the treated retina of LCA patients. The data revealed improvements and normalization along the visual fibers corresponding to the site of retinal injection of the gene therapy vector carrying the therapeutic gene in the treated eye compared to the visual pathway for the untreated eye of LCA patients. After gene therapy, the primary visual pathways (for example, geniculostriate fibers) in the treated retina were similar to those of sighted control subjects, whereas the primary visual pathways of the untreated retina continued to deteriorate. Our results suggest that visual experience, enhanced by gene therapy, may be responsible for the reorganization and maturation of synaptic connectivity in the visual pathways of the treated eye in LCA patients. The interactions between the eye and the brain enabled improved and sustained long-term visual function in patients with LCA after gene therapy

Expression profile of Wnt molecules in leukemic cells from Iranian patients with acute myeloblastic leukemia

Background: Wnt molecules play a key role in growth, proliferation and development of some embryonic and adult organs as well as hematopoietic stem cells. Wnt signaling pathways are aberrantly activated in many tumor types, including solid tumors and hematologic malignancies. Objective: To investigate the expression profile of a large number of Wnt genes in leukemic cells from Iranian patients with acute myeloblastic leukemia. Methods: RT-PCR method was used to determine the Wnt genes expression in bone marrow (BM) and/or peripheral blood (PB) samples from 16 patients with AML and PB samples of 36 normal subjects. Results: Among 14 Wnt molecules included in this study, Wnt-7A and Wnt-10A were significantly down-regulated (p = 0.002 and p < 0.0001, respectively) and Wnt-3 was significantly over-expressed (p < 0.02) in AML patients compared to normal subjects. No significant association was found between Wnt expression and FAB classification of the patients. Conclusion: Our results demonstrated for the first time aberrant expression of Wnt-7A, Wnt-10A and Wnt-3 genes in Iranian AML patients. This may be of relevance to the tumorigenesis process in this malignancy

Somatosensory and motor representations following bilateral transplants of the hands: A 6-year longitudinal case report on the first pediatric bilateral hand transplant patient

A vascularized composite tissue allotransplantation (VCA) was performed at the Children’s Hospital of Philadelphia (CHOP), on an 8-year-old patient in 2015, six years after bilateral hand and foot amputation. Hand VCA resulted in reafferentation of the medial, ulnar, and radial nerves serving hand somatosensation and motor function. We used magnetoencephalography (MEG) to assess somatosensory cortical plasticity following the post-transplantation recovery of the peripheral sensory nerves of the hands. Our 2-year postoperative MEG showed that somatosensory lip representations, initially observed at “hand areas”, reverted to canonical, orthotopic lip locations with recovery of post-transplant hand function. Here, we continue the assessment of motor and somatosensory responses up to 6-years post-transplant. Magnetoencephalographic somatosensory responses were recorded eight times over a six-year period following hand transplantation, using a 275-channel MEG system. Somatosensory tactile stimuli were presented to the right lower lip (all 8 visits) as well as right and left index fingers (visits 3-8) and fifth digits (visits 4-8). In addition, left and right-hand motor responses were also recorded for left index finger and right thumb (visit 8 only).During the acute recovery phase (visits 3 and 4), somatosensory responses of the digits were observed to be significantly larger and more phasic (i.e., smoother) than controls. Subsequent measures showed that digit responses maintain this atypical response profile (evoked-response magnitudes typically exceed 1 picoTesla). Orthotopic somatosensory localization of the lip, D2, and D5 was preserved. Motor beta-band desynchrony was age-typical in localization and response magnitude; however, the motor gamma-band response was significantly larger than that observed in a reference population.These novel findings show that the restoration of somatosensory input of the hands resulted in persistent and atypically large cortical responses to digit stimulation, which remain atypically large at 6 years post-transplant; there is no known perceptual correlate, and no reports of phantom pain. Normal somatosensory organization of the lip, D2, and D5 representation remain stable following post-recovery reorganization of the lip’s somatosensory response

Immunophenotypic subtyping of leukemic cells from Iranian patients with acute lymphoblastic leukaemia: Association to disease outcome

Background: Immunophenotypic characterization of the leukemic cells has been widely used as a tool for diagnosis, classification, stratification and prognosis of leukaemia. Objective: To investigate the immunophenotypic subtype profiles of Iranian patients with acute lymphoblastic leukemia (ALL) and its association to disease outcome. Methods: In this study, a total of 60 Iranian patients with ALL were immunophenotyped by flow cytometry using a panel of monoclonal antibodies specific for CD2, CD3, CD5, CD10, CD13, CD14, CD19, CD20, CD33, CD34, CD45, HLA-DR and TdT molecules. Results: The samples were initially categorized into T-ALL (n=9), B-ALL (n=50) and mixed lineage (n=1) based on the expression patterns of CD3 and CD19 molecules. B-ALL patients could further be classified into four subtypes, including Pro-B (n=7, 11.7), Pre-B I (n=28, 46.7), Pre-B II (n=13, 21.7) and immature/mature B cells (n=2, 3.3) on the basis of expression of CD10, CD19, CD20, HLA-DR and TdT. Clinical manifestations and laboratory findings of the patients did not reveal association with immunophenotypic subtypes of ALL, with the exception of mediastinal mass and WBC count at the time of diagnosis which were found to be significantly higher in patients with T-ALL compared with BALL (p=0.001 and 0.014), respectively. Conclusion: Our results indicate that overall the immunophenotypic profile of Iranian ALL patients is similar to previous reports and it might be used for monitoring of minimal residual disease and prognosis

Overexpression of orphan receptor tyrosine kinase Ror1 as a putative tumor-associated antigen in Iranian patients with acute lymphoblastic leukemia

Receptor tyrosine kinases (RTKs) are a group of enzymes involved in a variety of physiological and pathological processes. The human Ror1 is a member of the RTK family with unknown ligand and biological function. Overexpression of Ror1 has recently been reported in B-cell chronic lymphocytic leukemia. The aim of this study was to explore the expression profile of Ror1 in acute lymphoblastic leukemia (ALL) cells. Therefore, leukemic cells were isolated from the bone marrow and/or peripheral blood (PB) of 57 ALL patients. Immunophenotyping was performed by flow cytometry and mRNA expression was detected by RT-PCR. Overexpression of Ror1 mRNA was detected in 23 of 57 (40) ALL patients. A similar expression pattern was observed in ALL cell lines, with 4 of 12 (33) being positive. Stimulation of normal PB mononuclear cells with pokeweed mitogen and phorbol myristate acetate induced substantially higher Ror1 mRNA expression compared to unstimulated cultured cells. There has been neither a significant association between Ror1 expression and the immunophenotypic profile of the leukemic cells, nor with other clinical or hematological features of the patients. In conclusion, our findings propose Ror1 as a new tumor-associated antigen and a potential tool for targeted immunotherapy and monitoring of minimal residual disease in ALL. Copyright © 2008 S. Karger AG

Involvement of the spinal cord in primary mitochondrial disorders : a neuroimaging mimicker of inflammation and ischemia in children

CITATION: Alves, C. A. P. F. et al. 2021 . Involvement of the spinal cord in primary mitochondrial disorders : a neuroimaging mimicker of inflammation and ischemia in children. American Journal of Neuroradiology, 42(2):389-396, doi: 10.3174/ajnr.A6910.The original publication is available at: https://pubmed.ncbi.nlm.nih.govBackground and purpose: Little is known about imaging features of spinal cord lesions in mitochondrial disorders. The aim of this research was to assess the frequency, imaging features, and pathogenic variants causing primary mitochondrial disease in children with spinal cord lesions. Materials and methods: This retrospective analysis included patients seen at Children's Hospital of Philadelphia between 2000 and 2019 who had a confirmed diagnosis of a primary (genetic-based) mitochondrial disease and available MR imaging of the spine. The MR imaging included at least both sagittal and axial fast spin-echo T2-weighted images. Spine images were independently reviewed by 2 neuroradiologists. Location and imaging features of spinal cord lesions were correlated and tested using the Fisher exact test. Results: Of 119 children with primary mitochondrial disease in whom MR imaging was available, only 33 of 119 (28%) had available spine imaging for reanalysis. Nineteen of these 33 individuals (58%) had evidence of spinal cord lesions. Two main patterns of spinal cord lesions were identified: group A (12/19; 63%) had white ± gray matter involvement, and group B (7/19; 37%) had isolated gray matter involvement. Group A spinal cord lesions were similar to those seen in patients with neuromyelitis optica spectrum disorder, multiple sclerosis, anti-myelin oligodendrocyte glycoprotein-IgG antibody disease, and leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation. Group B patients had spinal cord findings similar to those that occur with ischemia and viral infections. Significant associations were seen between the pattern of lesions (group A versus group B) and the location of lesions in cervical versus thoracolumbar segments, respectively (P < .01). Conclusions: Spinal cord lesions are frequently observed in children with primary mitochondrial disease and may mimic more common causes such as demyelination and ischemia.Publisher's versio

Childhood acute lymphoblastic leukemia in the Middle East and neighboring countries: A prospective multi-institutional international collaborative study (CALLME1) by the Middle East Childhood Cancer Alliance (MECCA)

Background: Little is known about childhood ALL in the Middle East. This study was undertaken by MECCA as initial efforts in collaborative data collection to provide clinical and demographic information on children with ALL in the Middle East. Procedure: Clinical and laboratory data for patients with ALL between January 2008 and April 2012 were prospectively collected from institutions in 14 Middle East countries and entered into a custom-built-database during induction phase. All laboratory studies including cytogenetics were done at local institutions. Results: The 1,171 voluntarily enrolled patients had a mean age of 6.1±3.9 years and 59.2 were boys. T-ALL represented 14.8 and 84.2 had B-precursor ALL. At diagnosis, 5.6 had CNS disease. The distribution of common genetic abnormalities reflected a similar percentage of hyperdiploidy (25.6), but a lower percentage of ETV6-RUNX1 translocation (14.7) compared to large series reported from Western populations. By clinical criteria, 47.1 were low/standard risk, 16.9 were intermediate risk, and 36 were high risk. Most patients received all their care at the same unit (96.9). Patients had excellent induction response to chemotherapy with an overall complete remission rate of 96. Induction toxicities were acceptable. Conclusions: This first collaborative study has established a process for prospective data collection and future multinational collaborative research in the Middle East. Despite the limitations of an incomplete population-based study, it provides the first comprehensive baseline data on clinical characteristics, laboratory evaluation, induction outcome, and toxicity. Further work is planned to uncover possible biologic differences of ALL in the region and to improve diagnosis and management. Pediatr Blood Cancer 2014; 61:1403-1410. © 2014 Wiley Periodicals, Inc

The Brain Tumor Segmentation (BraTS) Challenge 2023: Focus on Pediatrics (CBTN-CONNECT-DIPGR-ASNR-MICCAI BraTS-PEDs)

Pediatric tumors of the central nervous system are the most common cause of cancer-related death in children. The five-year survival rate for high-grade gliomas in children is less than 20\%. Due to their rarity, the diagnosis of these entities is often delayed, their treatment is mainly based on historic treatment concepts, and clinical trials require multi-institutional collaborations. The MICCAI Brain Tumor Segmentation (BraTS) Challenge is a landmark community benchmark event with a successful history of 12 years of resource creation for the segmentation and analysis of adult glioma. Here we present the CBTN-CONNECT-DIPGR-ASNR-MICCAI BraTS-PEDs 2023 challenge, which represents the first BraTS challenge focused on pediatric brain tumors with data acquired across multiple international consortia dedicated to pediatric neuro-oncology and clinical trials. The BraTS-PEDs 2023 challenge focuses on benchmarking the development of volumentric segmentation algorithms for pediatric brain glioma through standardized quantitative performance evaluation metrics utilized across the BraTS 2023 cluster of challenges. Models gaining knowledge from the BraTS-PEDs multi-parametric structural MRI (mpMRI) training data will be evaluated on separate validation and unseen test mpMRI dataof high-grade pediatric glioma. The CBTN-CONNECT-DIPGR-ASNR-MICCAI BraTS-PEDs 2023 challenge brings together clinicians and AI/imaging scientists to lead to faster development of automated segmentation techniques that could benefit clinical trials, and ultimately the care of children with brain tumors