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Constitutional mismatch repair deficiency (CMMRD) is an aggressive and highly penetrant cancer predisposition syndrome. Because of its variable clinical presentation and phenotypical overlap with neurofibromatosis, timely diagnosis remains challenging, especially in countries with limited resources. Since current tests are either difficult to implement or interpret or both we used a novel and relatively inexpensive functional genomic assay (LOGIC) which has been recently reported to have high sensitivity and specificity in diagnosing CMMRD. Here we report the clinical and molecular characteristics of nine patients diagnosed with cancer and suspected to have CMMRD and highlight the challenges with variant interpretation and immunohistochemical analysis that led to an uncertain interpretation of genetic findings in 6 of the 9 patients. Using LOGIC, we were able to confirm the diagnosis of CMMRD in 7 and likely exclude it in 2 patients, resolving ambiguous result interpretation. LOGIC also enabled predictive testing of asymptomatic siblings for early diagnosis and implementation of surveillance. This study highlights the varied manifestations and practical limitations of current diagnostic criteria for CMMRD, and the importance of international collaboration for implementing robust and low-cost functional assays for resolving diagnostic challenges.
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Neoplasias Encefálicas , Neoplasias Colorretais , Humanos , Líbano , Neoplasias Encefálicas/diagnóstico , Neoplasias Colorretais/diagnóstico , Fenótipo , Genômica , GenótipoRESUMO
BACKGROUND: Oral mucositis (OM) is a significant complication occurring in approximately 40 to 80% of patients receiving chemotherapy regimens. Although a wide variety of agents have been tested to prevent OM or reduce its severity, none have provided conclusive evidence. OBJECTIVES: To determine the efficacy of honey or olive oil on the severity and OM pain in children with leukemia and suffering from OM compared to placebo (standard care) and, to assess which of the two interventions is more beneficial. METHODS: A single blind randomized controlled study (RCT) was used to evaluate the effect of Manuka honey or olive oil, in the treatment of chemotherapy-related OM in 42 children with leukemia. The primary outcome was the severity of mucositis, using the World Health Organization (WHO) scale and the secondary outcome was the pain assessed using the Visual analogue scale (VAS). RESULTS: Children who received the honey had less severe OM (assessed on the (WHO) scale), pâ¯=â¯0.00 and less pain (assessed on the VAS scale), pâ¯=â¯0.00, compared to the control group. Children who received the olive oil had less pain than the control group, pâ¯=â¯0.00), although not lower than the honey group. CONCLUSION: Manuka honey or olive oil can be used as alternative therapies by nurses to children with leukemia and suffering from OM, especially in low and middle-income countries where more expensive therapies may not be available or economical. PRACTICE IMPLICATIONS: Pediatric nurses may recommend Manuka honey to treat OM in children with leukemia as it is safe and inexpensive compared to other treatment modalities.
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Mel , Leucemia , Estomatite , Humanos , Criança , Azeite de Oliva/uso terapêutico , Estomatite/induzido quimicamente , Estomatite/tratamento farmacológico , Leucemia/complicações , DorRESUMO
Resource-limited settings often have financial barriers to genetic testing for heritable cancer. This retrospective study investigated the pattern of heritable cancer predisposition testing in a middle-income country over the period 2014-2021, excluding retinoblastoma. After establishing a specific fund in 2019, rate of tests increased from 1.1% to 10.9% of new diagnoses. Most common testing was for constitutional mismatch repair deficiency (CMMRD), rhabdoid predisposition syndrome, TP53 (tumor protein 53) mutation, and hereditary cancer panel. Of 33 patients, 13 (39%) tested positive, 12 (36%) negative, and eight (24%) had variants of unknown significance. Positivity rate was 43% for a clinical phenotype and 44% for a tumor type indication.
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Neoplasias Encefálicas , Neoplasias Colorretais , Síndromes Neoplásicas Hereditárias , Neoplasias da Retina , Retinoblastoma , Neoplasias Encefálicas/patologia , Neoplasias Colorretais/genética , Reparo de Erro de Pareamento de DNA , Predisposição Genética para Doença , Testes Genéticos , Humanos , Síndromes Neoplásicas Hereditárias/diagnóstico , Síndromes Neoplásicas Hereditárias/genética , Neoplasias da Retina/diagnóstico , Neoplasias da Retina/genética , Retinoblastoma/diagnóstico , Retinoblastoma/genética , Estudos RetrospectivosRESUMO
Vincristine is an essential component of rhabdomyosarcoma treatment. However, it can cause motor neurotoxicity, necessitating dose reductions. We retrospectively reviewed the rates and patterns of vincristine-induced motor neuropathy in children treated for rhabdomyosarcoma, and investigated effects on outcome. Fifteen of 43 patients (35%) developed motor neuropathies necessitating dose reductions, which ranged from 1.7% to 58% of planned cumulative dose. Older age was the only significant clinical risk factor. Almost half (47%) recovered during treatment with subsequent dose escalation. Most patients had complete resolution of symptoms upon follow-up. There was no discernible effect of treatment reduction on survival or relapse rates.
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Síndromes Neurotóxicas , Rabdomiossarcoma Embrionário , Rabdomiossarcoma , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Criança , Humanos , Recidiva Local de Neoplasia/tratamento farmacológico , Síndromes Neurotóxicas/etiologia , Estudos Retrospectivos , Rabdomiossarcoma/complicações , Vincristina/efeitos adversosRESUMO
OBJECTIVE: To determine the prevalence and to characterize the different types of strokes in children with cancer at the Children's Cancer Center of Lebanon (CCCL), in addition to assess the factors and clinical findings leading to stroke in children. METHODS: We retrospectively reviewed the medical records and brain images (MRIs and CTs) of children admitted to the CCCL and diagnosed with cancer between years 2008 and 2017. Brain images were reviewed for the strokes' onset, size, location, possible origin, its recurrence and type: intracranial hemorrhage (ICH), acute arterial ischemic stroke, and cerebral sinus venous thrombosis (CSVT) with and without venous infarct. Medical charts of the patients were reviewed for age, sex, their type of cancer, the treatment protocol they followed, and abnormal findings on their laboratory studies and neurological exams. RESULTS: Out of the 905 charts reviewed, twenty-seven children with variable types of cancer had strokes, with a prevalence of 2.9%. Their median age at cancer diagnosis was 9.4 (4.8-13.7) years and the median age at stroke onset was 10.6 (6.7-15.5) years. The median time between the cancer diagnosis and the stroke episode was 6 months. CSVT cases were the most common (60%) followed by acute arterial ischemic (22%) and hemorrhagic strokes (18%), with CSVT being the latest to occur. We observed that the different types of strokes were related to some types of cancer. Of the children that had acute arterial ischemic stroke in this cohort, 83% had brain tumors, of the children who had CSVT, 87.5% had leukemia, and of the children who had hemorrhagic stroke, 40% had leukemia. Neurological abnormalities were more prevalent in acute arterial ischemic stroke (80%). Patients with CSVT recovered better than those with other types of strokes. Strokes recurred in 60% of ischemic strokes. L-Asparaginase was significantly associated with CSVT. CONCLUSIONS: The prevalence of strokes was 2.9% in children with cancer. We were able to identify factors related to the types of the stroke that occurred in children including the type and location of the cancer the type of treatment received, and stroke recurrence.
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Isquemia Encefálica , Neoplasias , Acidente Vascular Cerebral , Criança , Humanos , Hemorragias Intracranianas , Neoplasias/complicações , Neoplasias/epidemiologia , Prevalência , Estudos Retrospectivos , Fatores de Risco , Acidente Vascular Cerebral/epidemiologiaRESUMO
Expandable endoprostheses provide a limb salvage option for skeletally immature patients with bone sarcoma of the lower extremities. Initial reports of the Repiphysis prosthesis were encouraging; however, medium-term follow-up revealed high complication rates. We report on the long-term follow-up of a cohort of patients treated with the Repiphysis prosthesis. Eleven patients were included in the study. Data collected included sex, age at surgery, duration of follow-up, site of disease, histologic diagnosis, number of lengthening sessions, amount lengthened, postoperative complications, endoprosthetic failure, mode of endoprosthetic failure, duration from index surgery to failure and to revision, type of revision surgery and final limb-length discrepancy. The average duration of follow-up from the time of surgery was 180 months (range, 144-215 months). Fifteen Repiphysis implants were used in 11 patients. All implants failed with an average time from surgery to failure of 36 months (range, 3-72 months). Twenty-four complications were observed: one wound dehiscence, two deep infections, 18 mechanical failures, implant collapse with destruction of proximal tibia epiphysis in two and one periprosthetic proximal femur fracture with dislodgement of the stem. Despite being an option for limb salvage, the Repiphysis prosthesis has a high rate of mechanical failure and need for revision, similar to other expandable implants. The authors, therefore, recommend full disclosure of the potential short- and long-term complications and need for revision, as well as alternative treatment options if their use is considered. Level of evidence: IV (Therapeutic).
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Neoplasias Ósseas , Neoplasias Femorais , Sarcoma , Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/cirurgia , Criança , Neoplasias Femorais/cirurgia , Seguimentos , Humanos , Salvamento de Membro , Extremidade Inferior , Desenho de Prótese , Falha de Prótese , Implantação de Prótese , Estudos Retrospectivos , Sarcoma/diagnóstico por imagem , Sarcoma/cirurgia , Resultado do TratamentoRESUMO
Aim: To evaluate the association between candidate genetic polymorphisms and glucocorticoid-induced osteonecrosis in Arab children treated for acute lymphoblastic leukemia. Methods: A total of 189 children treated for acute lymphoblastic leukemia were genotyped for four SNPs with allele discrimination assays. The incidence and timing of radiologically confirmed symptomatic grade 4 osteonecrosis were classified based on the Ponte di Legno toxicity working group consensus definition. Results: Thirteen children developed grade 4 osteonecrosis (6.8%), of whom 12 received the intermediate/high-risk treatment protocol. GRIN3A variant allele carriers had to stop dexamethasone therapy earlier resulting in significantly shorter duration of dexamethasone treatment (mean [95% CI]: 75.17 [64.28-86.06] vs 85.90 [81.22-90.58] weeks; p = 0.054) and lower cumulative dose (mean [95% CI]: 1118.11 [954.94-1281.29] vs 1341.14 [1264.17-1418.11] mg/m2; p = 0.011). Conclusion: This is the first pharmacogenomics evaluation of the association between GRIN3A variants and glucocorticoid-induced osteonecrosis in Arab children.
Lay abstract This study aimed at uncovering variants in the genetic material of Arab children, that might predispose them to develop a specific treatment-related adverse effect, during their therapy for acute lymphoblastic leukemia (a type of blood cancer). We looked at specific changes in the DNA of our patient cohort that might predispose them to develop treatment-induced osteonecrosis. Osteonecrosis is by definition a loss of blood flow to the bone tissue in one's body, causing the bone to die. Osteonecrosis may be caused by long-term exposure to steroid-based medication, among which dexamethasone. Dexamethasone a main component of the combination of chemotherapeutic agents used to treat acute lymphoblastic leukemia. Our findings suggested that children who had one of the variants detected in a specific location of DNA, the GRIN3A gene, were more likely to develop osteonecrosis earlier and had to stop dexamethasone earlier during therapy.
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Osteonecrose , Leucemia-Linfoma Linfoblástico de Células Precursoras , Criança , Genótipo , Glucocorticoides/efeitos adversos , Humanos , Osteonecrose/induzido quimicamente , Osteonecrose/genética , Polimorfismo de Nucleotídeo Único/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Receptores de N-Metil-D-AspartatoRESUMO
BACKGROUND: Cerebral sinus venous thrombosis (CSVT) is one of the many side effects encountered during acute lymphoblastic leukemia (ALL) therapy. Due to the rarity of cases, lack of data, and consensus management, no recommendations exist to target the population at risk. METHODS: This is a retrospective chart review of 229 consecutive patients diagnosed with ALL with an age range of 1-21 years, treated at the Children's Cancer Center of Lebanon between October 2007 and February 2018. RESULTS: The incidence of CSVT was 10.5%. Using univariate analysis, increased risk of CSVT was observed with male gender, age >10 years, T-cell immunophenotype, intermediate/high-risk disease, maximum triglyceride (TG) level of >615 mg/dl, presence of mediastinal mass, and larger body surface area (BSA). With multivariate analysis, the only statistically significant risk factors were maximum TG level, BSA, presence of mediastinal mass, and risk stratification (intermediate/high risk). CONCLUSION: Our study was able to unveil TG level of >615 mg/dl, mediastinal mass, and a larger BSA as novel risk factors that have not been previously discussed in the literature.
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Leucemia-Linfoma Linfoblástico de Células Precursoras , Trombose dos Seios Intracranianos , Trombose Venosa , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Incidência , Lactente , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicações , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Estudos Retrospectivos , Fatores de Risco , Trombose dos Seios Intracranianos/epidemiologia , Trombose dos Seios Intracranianos/etiologia , Trombose Venosa/epidemiologia , Trombose Venosa/etiologia , Adulto JovemRESUMO
BACKGROUND: Viral infections in children and adolescents with malignancy are commonly encountered and have a significant impact on morbidity and mortality. Studies and epidemiological data regarding viral infections in children with cancer in developing countries are lacking. This retrospective cohort study aims to assess the burden of viral infections in children and adolescents with cancer, by assessing prevalence, risk factors, as well as morbidity and mortality of common viruses over a period of 8 years. METHODS AND FINDINGS: Medical records of cancer patients treated at the Children Cancer Center of Lebanon were reviewed and 155 participants under the age of 21 were identified with at least one documented viral infection during the period from July 2009 to November 2017. This subset included 136 participants with active malignancy and 19 participants with a history of cancer who underwent hematopoietic stem cell transplantation [HSCT] and were in remission; the latter group was analyzed separately. Information regarding participant characteristics, hospital course, and complications were obtained. Associations between viral infections and certain factors were assessed. In the cohort, 64% were male, 81% were Lebanese. In participants with active malignancy, 90% received chemotherapy in the 6 months preceding the viral infection episode, 11% received radiotherapy. 51% of participants were neutropenic at the time of viral detection, and 77% were lymphopenic. 17% experienced a bacterial co-infection, and 3 experienced a viral co-infection. Among 162 viral infection episodes, clinically diagnosed skin infections, mainly herpes simplex virus type 1 and varicella-zoster virus, were the most common [44% of cases]. These were followed by laboratory-proven systemic herpes infections: cytomegalovirus [14%] and Epstein-Barr virus [6%]. Respiratory viruses: influenza and respiratory syncytial virus, accounted for 9% and 4%, respectively, whereas rotavirus represented 11% and BK virus represented 3% of cases. Acute lymphocytic leukemia was the most prevalent neoplasia [57%]. Fever was the most common presenting symptom [55%] and febrile neutropenia was the reason for admission in 24% of cases. The mean length of stay was significantly longer in participants with cytomegalovirus infections and significantly lower in rotavirus infection. Admission to the ICU occurred in 9%, complications in 8%, and mortality in 5%. Participants with viral infections post-HSCT were noted to have a significantly longer length of hospital stay compared to non-HSCT participants, with no other significant differences in clinical course and outcome. The study was limited by its retrospective nature and by the late introduction and underuse of multiplex PCR panels, which may have led to underdiagnosis of viral infections. CONCLUSIONS: Viral infections were prevalent in our sample of cancer patients and may have contributed to morbidity and mortality. Newly available viral diagnostics are likely to vastly increase the number and scope of detectable viral infections in this population. Prospective studies using multiplex PCR technology with systematic testing of patients will be more helpful in defining the burden of viral infections. Furthermore, efforts at antimicrobial stewardship would benefit from the identification of viral causes of infection and limit the unnecessary use of antibiotics in the pediatric cancer population.
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Infecções por Citomegalovirus/epidemiologia , Influenza Humana/epidemiologia , Neoplasias/epidemiologia , Infecções Respiratórias/epidemiologia , Adolescente , Criança , Criança Hospitalizada , Pré-Escolar , Coinfecção/complicações , Coinfecção/diagnóstico , Coinfecção/virologia , Infecções por Citomegalovirus/complicações , Infecções por Citomegalovirus/diagnóstico , Infecções por Citomegalovirus/virologia , Feminino , Transplante de Células-Tronco Hematopoéticas , Hospitais , Humanos , Lactente , Influenza Humana/complicações , Influenza Humana/diagnóstico , Influenza Humana/virologia , Líbano/epidemiologia , Reação em Cadeia da Polimerase Multiplex/métodos , Neoplasias/complicações , Neoplasias/diagnóstico , Neoplasias/virologia , Pediatria , Vírus Sincicial Respiratório Humano/genética , Vírus Sincicial Respiratório Humano/isolamento & purificação , Vírus Sincicial Respiratório Humano/patogenicidade , Infecções Respiratórias/complicações , Infecções Respiratórias/diagnóstico , Infecções Respiratórias/virologia , Estudos Retrospectivos , Infecções por Rotavirus/complicações , Infecções por Rotavirus/diagnóstico , Infecções por Rotavirus/epidemiologia , Infecções por Rotavirus/patologiaRESUMO
Despite major advances in the management and high cure rates of childhood acute lymphoblastic leukemia (ALL), patients still suffer from many drug-induced toxicities, sometimes necessitating dose reduction, or halting of cytotoxic drugs with a secondary risk of disease relapse. In addition, investigators have noted significant inter-individual variability in drug toxicities and disease outcomes, hence the role of pharmacogenetics (PGx) in elucidating genetic polymorphisms in candidate genes for the optimization of disease management. In this review, we present the PGx data in association with main toxicities seen in children treated for ALL in addition to efficacy, with a focus on the most plausible germline PGx variants. We then follow with a summary of the highest evidence drug-gene annotations with suggestions to move forward in implementing preemptive PGx for the individualization of treatment regimens for children with ALL.
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BACKGROUND: Childhood cancer is a highly curable disease when timely diagnosis and appropriate therapy are provided. A negative impact of the coronavirus disease 2019 (COVID-19) pandemic on access to care for children with cancer is likely but has not been evaluated. METHODS: A 34-item survey focusing on barriers to pediatric oncology management during the COVID-19 pandemic was distributed to heads of pediatric oncology units within the Pediatric Oncology East and Mediterranean (POEM) collaborative group, from the Middle East, North Africa, and West Asia. Responses were collected on April 11 through 22, 2020. Corresponding rates of proven COVID-19 cases and deaths were retrieved from the World Health Organization database. RESULTS: In total, 34 centers from 19 countries participated. Almost all centers applied guidelines to optimize resource utilization and safety, including delaying off-treatment visits, rotating and reducing staff, and implementing social distancing, hand hygiene measures, and personal protective equipment use. Essential treatments, including chemotherapy, surgery, and radiation therapy, were delayed in 29% to 44% of centers, and 24% of centers restricted acceptance of new patients. Clinical care delivery was reported as negatively affected in 28% of centers. Greater than 70% of centers reported shortages in blood products, and 47% to 62% reported interruptions in surgery and radiation as well as medication shortages. However, bed availability was affected in <30% of centers, reflecting the low rates of COVID-19 hospitalizations in the corresponding countries at the time of the survey. CONCLUSIONS: Mechanisms to approach childhood cancer treatment delivery during crises need to be re-evaluated, because treatment interruptions and delays are expected to affect patient outcomes in this otherwise largely curable disease.
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COVID-19 , Neoplasias/terapia , África do Norte/epidemiologia , Ásia Ocidental/epidemiologia , COVID-19/epidemiologia , Criança , Estudos Transversais , Atenção à Saúde , Pessoal de Saúde/organização & administração , Pessoal de Saúde/estatística & dados numéricos , Hospitais/estatística & dados numéricos , Humanos , Oriente Médio/epidemiologia , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Healthcare providers' perceptions of palliative care in children with cancer influence care management, specifically that of its early integration. Thus, it is crucial to understand the perspectives of the providers on early integration of palliative care so that measures to create informed care decisions are based on reconciling their views. AIMS: To explore the perceptions of paediatric oncology providers at the Children's Cancer Institute (CCI) in Lebanon regarding the integration of early paediatric palliative care (PPC) in the management of children with cancer. METHODS: A qualitative descriptive research design with focus groups was used in a leading paediatric oncology setting. FINDINGS: The thematic analysis yielded four themes: (1) healthcare providers understood palliative care as pain relief and psychological support mainly at the end of life; (2) the timing of integrating PPC is linked to end of life, advanced disease or treatment failure; (3) interdisciplinary collaboration is important for addressing patients' and families' needs effectively; and (4) communication with the child and family is one of the most difficult aspects of integrating PPC. CONCLUSION: This study demonstrated the perceptions of healthcare providers about early palliative care in paediatric oncology in Lebanon. It also highlighted the importance of interdisciplinary collaboration and effective communication with the child and family for better management of PPC.
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Pessoal de Saúde/psicologia , Enfermagem de Cuidados Paliativos na Terminalidade da Vida/normas , Neoplasias/enfermagem , Cuidados Paliativos/psicologia , Cuidados Paliativos/normas , Pediatria/normas , Guias de Prática Clínica como Assunto , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Grupos Focais , Humanos , Lactente , Recém-Nascido , Líbano , Masculino , Pessoa de Meia-Idade , Pesquisa QualitativaRESUMO
The aim of this trial was to decrease the incidence of life-threatening infections by decreasing the dose and the duration of dexamethasone treatment during maintenance therapy. This was a prospective, nonrandomized trial of low-risk acute lymphoblastic leukemia patients 1 to 18 years of age who were treated at the Children's Cancer Center of Lebanon (CCCL). Patients consecutively diagnosed between 2002 and 2013 were divided into groups 1 and 2 receiving total dexamethasone doses of 1144 and 618 mg/m, respectively. A total of 84 patients were assigned to group 1 and 33 patients to group 2. The 5-year cumulative incidence of isolated central nervous system relapse increased from (n=0% [95% confidence interval: 0%-4.4%]) in group 1 to 9.1% [95% confidence interval: 3%-23%]; P=0.021) in group 2. Decreasing cumulative dose of dexamethasone for low-risk childhood acute lymphoblastic leukemia patients aiming to avoid serious viral infections led to a significant increase in isolated central nervous system relapse.
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Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias do Sistema Nervoso Central/epidemiologia , Recidiva Local de Neoplasia/epidemiologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Adolescente , Estudos de Casos e Controles , Neoplasias do Sistema Nervoso Central/induzido quimicamente , Neoplasias do Sistema Nervoso Central/diagnóstico , Criança , Pré-Escolar , Dexametasona/administração & dosagem , Relação Dose-Resposta a Droga , Feminino , Seguimentos , Humanos , Incidência , Lactente , Líbano/epidemiologia , Masculino , Metotrexato/administração & dosagem , Recidiva Local de Neoplasia/induzido quimicamente , Recidiva Local de Neoplasia/diagnóstico , Ensaios Clínicos Controlados não Aleatórios como Assunto , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Prognóstico , Estudos Prospectivos , Taxa de SobrevidaRESUMO
Background: Acute lymphoblastic leukemia (ALL) is the most common cancer seen in children worldwide and in the Middle East. Although there have been major advances in treatment approaches for childhood ALL, serious toxicities do occur but with significant inter-individual variability. The aim of this study is to measure the frequency of polymorphisms in candidate genes involved in 6-Mercaptopurine (6-MP) disposition in a combined cohort of Middle Eastern Children with ALL, and evaluate whether these polymorphisms predict 6-MP intolerance and toxicity during ALL maintenance therapy. Methods: The study includes children treated for ALL on two treatment protocols from two cohorts; one from Lebanon (N = 136) and another from Kurdistan province of Iran (N = 74). Genotyping for the following six candidate genetic polymorphisms: ITPA 94C > A (rs1127354) and IVS2+21A > C (rs7270101), TPMT*2 238G > C (rs1800462), TPMT*3B 460G > A (rs1800460) and *3C 719A > G (rs1142345), and NUDT15 415C > T (rs116855232) was performed and analyzed in association with 6-MP dose intensity and toxicity. Results: As expected, TPMT and NUDT15 variants were uncommon. As for ITPA, both polymorphisms were more common in the Lebanese as compared to the Kurdish cohort with a minor allele frequency of 0.05 for 94C > A and 0.14 for IVS2+21A > C in the Lebanese only (N = 121), and of 0.01 for either ITPA polymorphism in Kurds. The most significant toxic effects were depicted with the NUDT15 polymorphism with a median 6-MP dose intensity of 33.33%, followed by 46.65% for TPMT*3A polymorphism, followed by 65.33% for two ITPA risk allele carriers and 74% for one ITPA risk allele carriers, in comparison to a median of 100% for the homozygous wild type in the combined cohort (P < 0.001). In addition, the onset of febrile neutropenia was significantly higher in variant allele carriers in the combined cohorts. Conclusions: These data confirm the predictive role of TPMT, NUDT15, and ITPA in 6-MP intolerance in Middle Eastern children with ALL. Given the relatively high frequency of ITPA variants in our study and their significant association with 6-MP dose intensity, we recommend that physicians consider genotyping for ITPA variants in conjunction with TPMT and NUDT15 prior to 6-MP therapy in these children.
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Retinoblastoma is an ocular tumor that occurs in young children, in either heritable or sporadic manner. The relative rarity of retinoblastoma, and the need for expensive equipment, anesthesia, and pediatric ophthalmologic expertise, are barriers for effective treatment in developing countries. Also, with an average age-adjusted incidence of two to five cases per million children, patient number limits development of local expertise in countries with small populations. Lebanon is a small country with a population of approximately 4.5 million. In 2012, a comprehensive retinoblastoma program was formalized at the Children's Cancer Institute (CCI) at the American University of Beirut Medical Center, and resources were allocated for efficient interdisciplinary coordination to attract patients from neighboring countries such as Syria and Iraq, where such specialized therapy is also lacking. Through this program, care was coordinated across hospitals and borders such that patients would receive scheduled chemotherapy at their institution, and monthly retinal examinations and focal laser therapy at the CCI in Lebanon. Our results show the feasibility of successful collaboration across borders, with excellent patient and physician adherence to treatment plans. This was accompanied by an increase in patient referrals, which enables continued expertise development. However, the majority of patients presented with advanced intraocular disease, necessitating enucleation in 90% of eyes in unilateral cases, and more than 50% of eyes in bilateral cases. Future efforts need to focus on expanding the program that reaches to additional hospitals in both countries, and promoting early diagnosis, for further improvement of globe salvage rates.
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Institutos de Câncer/organização & administração , Países em Desenvolvimento , Hospitais Universitários/organização & administração , Internacionalidade , Colaboração Intersetorial , Neoplasias da Retina/terapia , Retinoblastoma/terapia , Institutos de Câncer/economia , Terapia Combinada/economia , Terapia Combinada/métodos , Diagnóstico Tardio , Gerenciamento Clínico , Estudos de Viabilidade , Feminino , Aconselhamento Genético , Hospitais Universitários/economia , Humanos , Incidência , Lactente , Recém-Nascido , Estimativa de Kaplan-Meier , Líbano/epidemiologia , Masculino , Oriente Médio/epidemiologia , Equipe de Assistência ao Paciente , Encaminhamento e Consulta , Neoplasias da Retina/diagnóstico , Neoplasias da Retina/epidemiologia , Retinoblastoma/diagnóstico , Retinoblastoma/economia , Retinoblastoma/epidemiologia , Resultado do Tratamento , Estados UnidosRESUMO
PURPOSE: Outcomes in pediatric osteosarcoma have dramatically improved over the past few decades, with overall survival rates of 70% and 30% for patients with localized and metastatic disease, respectively. PATIENTS AND METHODS: We retrospectively reviewed clinical characteristics and outcomes of 38 patients treated between 2001 and 2012 at a single institution in Lebanon. All patients received a uniform three-drug chemotherapy regimen consisting of cisplatin, doxorubicin, and methotrexate. Ifosfamide and etoposide were added to the adjuvant treatment regimen in case of metastatic disease and/or poor degree of tumor necrosis (< 90%). RESULTS: After a median follow-up of 61 months (range, 8 to 142 months), patients with localized disease had 5-year overall and event-free survival rates of approximately 81% and 68%, respectively, whereas for metastatic disease, they were approximately 42%. The most common primary site was the long bones around the knee (n = 34; 89.5%). Six patients (15.8%) had metastatic disease to lungs, and three (7.9%) had synchronous multifocal bone disease with lung metastases. Adverse prognostic factors included nonlower extremity sites, metastasis, poor degree of necrosis, and delay of more than 4 weeks in local control. In bivariable analysis, only degree of necrosis was a prognostic predictor for survival and disease recurrence. CONCLUSION: Treatment of pediatric osteosarcoma in a multidisciplinary cancer center in Lebanon resulted in survival similar to that in developed countries. Delay in local control was associated with worse outcome. The only statistically significant inferior outcome predictor was poor degree of necrosis at the time of local control.
Assuntos
Neoplasias Ósseas/terapia , Cisplatino/uso terapêutico , Doxorrubicina/uso terapêutico , Etoposídeo/uso terapêutico , Metotrexato/uso terapêutico , Osteossarcoma/terapia , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Ósseas/mortalidade , Criança , Pré-Escolar , Intervalo Livre de Doença , Feminino , Humanos , Lactente , Líbano , Masculino , Terapia Neoadjuvante , Metástase Neoplásica , Osteossarcoma/mortalidade , Prognóstico , Estudos Retrospectivos , Medição de Risco , Resultado do TratamentoRESUMO
BACKGROUND: Patients with pediatric cancer have a higher risk of morbidity and mortality because of respiratory viral infections than other patient populations. OBJECTIVES: To investigate the causative viruses of respiratory infections and their burden among patients with pediatric cancer in Lebanon. STUDY DESIGN: Nasopharyngeal swabs along with clinical and demographic data were collected from patients with pediatric cancer presenting febrile episodes with upper respiratory tract symptoms. Total nucleic acid was extracted from specimens followed by the real-time PCR analysis targeting 14 respiratory viruses to estimate the frequency of infections. RESULTS: We obtained 89 nasopharyngeal swabs from patients with pediatric cancer (mean age, 5.8 ± 4.2 years). Real-time PCR confirmed viral infection in 77 swabs (86.5%). Among these, 151 respiratory viruses were detected. Several viruses cocirculated within the same period; respiratory syncytial virus (RSV) being the most common (45.45%), followed by parainfluenza virus (PIV; 26%), influenza type B (26%), human metapneumovirus (24.6%), and human coronavirus (HCoV; 24.6%). Coinfections were detected in 55% of the subjects, and most of them involved RSV with one or more other viruses. A strong correlation was found between PIV, Flu (influenza of any type), RSV, and HCoV with the incidence of coinfections. RSV was associated with lower respiratory tract infections, nasal congestion, bronchitis, and bacteremia. HCoV was associated with bronchiolitis; rhinovirus was associated with hospital admission. CONCLUSION: Patients with pediatric cancer have a high burden of respiratory viral infections and a high incidence of coinfections. Molecular diagnostics can improve management of febrile episodes and reduce antibiotic use.
Assuntos
Neoplasias/complicações , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/virologia , Viroses/epidemiologia , Vírus/isolamento & purificação , Doença Aguda/epidemiologia , Criança , Pré-Escolar , Coinfecção/epidemiologia , Coinfecção/virologia , Feminino , Humanos , Hospedeiro Imunocomprometido , Incidência , Lactente , Recém-Nascido , Masculino , Neoplasias/virologia , Prevalência , Vírus/classificaçãoRESUMO
Melorheostosis, also known as Leri's disease, is a rare benign form of mesodermal mixed sclerosing bone dysplasia. We report the unusual case of a 14-year-old boy with melorheostosis in the lower extremity that went undiagnosed due to concurrent Ewing sarcoma in the opposite limb, confounding the findings for metastatic disease. The diagnosis was made on FDG PET/CT when the patient presented for post Ewing sarcoma treatment follow-up. The different types of melorheostosis as well as the challenge of diagnosing this rare entity are discussed in this report.
Assuntos
Doenças do Desenvolvimento Ósseo/diagnóstico por imagem , Melorreostose/diagnóstico por imagem , Tíbia , Adolescente , Doenças do Desenvolvimento Ósseo/patologia , Humanos , Masculino , Melorreostose/patologia , Tomografia por Emissão de Pósitrons combinada à Tomografia ComputadorizadaRESUMO
INTRODUCTION: Tonsillectomy and adenoidectomy (T& A) are the most common pediatric surgical procedures performed world-wide. Bleeding remains the most common complication of these procedures with 1-5.7% prevalence. METHODS: We recruited 1269 patients who were scheduled for either tonsillectomy, adenoidectomy or both. All patients had preoperative CBC, PT, and aPTT ordered. According to the results, patients were labelled as either "abnormal group" or "normal group". RESULTS: 35 patients had abnormal lab results 18 of these patients were diagnosed with coagulation disorders on further laboratory testing.9 of these patients had no pertinent history of bleeding. Even though an association is noted between abnormal lab tests and preoperative history of risk of bleeding, the correlation did not have high sensitivity (28.6%). CONCLUSION: This study provides evidence that preoperative history can give some information on patients with abnormal coagulation profile but may underestimate the prevalence of such diseases. In addition, patients with abnormal coagulation profile have more risk of postoperative bleeding even after adequate medical treatment perioperative. Thus, identifying these patients will help the clinician in providing the best surgical management with the least morbidity and mortality.