Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 40
Filter
1.
BDJ Open ; 9(1): 3, 2023 Feb 07.
Article in English | MEDLINE | ID: mdl-36750718

ABSTRACT

AIM: To explore oral health-related knowledge, abilities, attitudes, practices, and barriers of pediatric oncology nurses at an Asian children's hospital. METHODS: A cross-sectional study was conducted via a self-administered anonymized questionnaire. Data was analyzed to summarize knowledge, confidence, and practice behaviors. RESULTS: All sixty-three pediatric oncology nurses responded. Fifteen participants had >80% of the knowledge questions correct. Majority (97.3%) agreed on their roles in helping patients maintain their oral health. However, 75.8% of participants felt need for training in giving oral health advice. Notably, 74.6% checked patients' mouths at least once daily but only 57.1% felt adequately trained. Though a high proportion (>90%) of nurses felt confident to assist with oral care, only 65% would assist patients to do so; "Uncooperative patient" was the major barrier reported. DISCUSSION: Nurses have high general awareness of importance of oral health, but had incomplete knowledge. Compared to previous studies, most (90.5%) did not find performing oral care unpleasant but other barriers might have hindered actual oral care practice. CONCLUSION: Nurses were motivated to assist in oral care of children with cancer but sometimes felt ill-equipped. Updated national and institution guidelines, didactic and hands-on training, and implementation of practical support could be considered.

5.
J Intensive Care Med ; 37(4): 555-564, 2022 Apr.
Article in English | MEDLINE | ID: mdl-34396806

ABSTRACT

BACKGROUND: There is an increasing frequency of oncology and hematopoietic stem cell transplant (HSCT) patients seen in the intensive care unit and requiring extracorporeal membrane oxygenation (ECMO), however, prognosis of this population over time is unclear. METHODS: MEDLINE, EMBASE, Cochrane and Web of Science were searched from earliest publication until April 10, 2020 for studies to determine the mortality trend over time in oncology and HSCT patients requiring ECMO. Primary outcome was hospital mortality. Random-effects meta-analysis model was used to obtain pooled estimates of mortality and 95% confidence intervals. A priori subgroup metanalysis compared adult versus pediatric, oncology versus HSCT, hematological malignancy versus solid tumor, allogeneic versus autologous HSCT, and veno-arterial versus veno-venous ECMO populations. Multivariable meta-regression was also performed for hospital mortality to account for year of study and HSCT population. RESULTS: 17 eligible observational studies (n = 1109 patients) were included. Overall pooled hospital mortality was 72% (95% CI: 65, 78). In the subgroup analysis, only HSCT was associated with a higher hospital mortality compared to oncology subgroup [84% (95% CI: 70, 93) vs. 66% (95% CI: 56, 74); P = 0.021]. Meta-regression showed that HSCT was associated with increased mortality [adjusted odds ratio (aOR) 3.84 (95% CI 1.77, 8.31)], however, mortality improved with time [aOR 0.92 (95% CI: 0.85, 0.99) with each advancing year]. CONCLUSION: This study reports a high overall hospital mortality in oncology and HSCT patients on ECMO which improved over time. The presence of HSCT portends almost a 4-fold increased risk of mortality and this finding may need to be taken into consideration during patient selection for ECMO.


Subject(s)
Extracorporeal Membrane Oxygenation , Hematologic Neoplasms , Hematopoietic Stem Cell Transplantation , Neoplasms , Adult , Child , Extracorporeal Membrane Oxygenation/adverse effects , Hematopoietic Stem Cell Transplantation/adverse effects , Humans , Intensive Care Units , Neoplasms/etiology , Neoplasms/therapy
6.
J Paediatr Child Health ; 58(3): 392-396, 2022 Mar.
Article in English | MEDLINE | ID: mdl-34553811

ABSTRACT

AIM: This study aimed to review the use of medications in a paediatric palliative care (PPC) population during the last two weeks of life. METHODS: This is a retrospective observational cohort study that included 50 consecutive patients who were referred to KK Hospital PPC service from 2011 to 2015. Those who died after two weeks from discharge date were excluded. Medication charts were reviewed and relevant data were extracted. RESULTS: The study population included 42 patients and consists predominantly oncological and neurological diagnoses. The median number of medications used was 11.5. Ninety-five percent (40 out of 42) of study population required analgesia where 81% (34 out of 42) were opioid. There was prevalent use of antibiotics (86% of study population, 36 out of 42). Less frequently used medications included steroids, sedatives, laxatives and antiemetics (48%, 52%, 48% and 38% of study population respectively). CONCLUSION: Significant number of medications was used in PPC during the last two weeks of life. Apart from significant use of analgesia, there is also notable use of antibiotics. Future directions in education such as prescription of laxatives with opioid are proposed.


Subject(s)
Analgesics, Opioid , Palliative Care , Analgesics, Opioid/therapeutic use , Child , Cohort Studies , Death , Humans , Retrospective Studies
7.
Healthcare (Basel) ; 9(12)2021 Dec 20.
Article in English | MEDLINE | ID: mdl-34946487

ABSTRACT

The aim of this study was to explore the benefits of music therapy (MT) for children with cancer over the course of their treatment in an acute paediatric hospital setting in Singapore. Twenty-five children undergoing cancer treatment received MT sessions as part of a multidisciplinary team rehabilitation intervention from March 2017 to January 2020. A total of 37 individualised goals were developed by the music therapist for the cohort. Goals were scored via the Goal Attainment Scale at 3-month intervals up to 1 year. Descriptive statistics and correlation analysis were used to evaluate the findings. The rate of goal achievement was 89.2% over 180 MT sessions (M = 7.20, SD = 6.45). Children diagnosed with brain tumours had the highest frequency of MT sessions (M = 9.11, SD = 7.79). Most of the goals targeted the regulation of mood and morale through music. There was a positive correlation found between goals and sessions (rs = 0.56, p = 0.004). Age of the children was not correlated with the number of sessions received (rs= -0.19, p = 0.354). MT has been found to be an accessible and effective intervention in addressing functional and emotional goals for children across all ages who are undergoing cancer treatment.

8.
BMJ Case Rep ; 14(4)2021 Apr 16.
Article in English | MEDLINE | ID: mdl-33863770

ABSTRACT

A Chinese male infant was born at 35 weeks weighing 2935 g to a mother with polyhydramnios and prenatal hydrops fetalis. He developed marked respiratory distress secondary to bilateral congenital chylothorax and required pleural drainage, high frequency oscillation and inhaled nitric oxide therapy. He was extubated to non-invasive ventilation by day 14. There was no bacterial or intrauterine infection, haematologic, chromosomal or cardiac disorder. He was exclusively fed medium-chain triglyceride formula. High-resolution CT showed diffuse interstitial lung disease. He received a dexamethasone course for chronic lung disease to facilitate supplemental oxygen weaning. A multidisciplinary team comprising neonatology, pulmonology, haematology, interventional radiology and thoracic surgery considered congenital pulmonary lymphangiectasia as the most likely diagnosis and advised open lung biopsy, lymphangiography or scintigraphy for diagnostic confirmation should symptoms of chylothorax recur. Fortunately, he was weaned off oxygen at 5 months of life, and tolerated human milk challenge at 6 months of life and grew well.


Subject(s)
Chylothorax , Hydrops Fetalis , Lung Diseases, Interstitial , Chylothorax/complications , Chylothorax/congenital , Chylothorax/diagnosis , Humans , Hydrops Fetalis/etiology , Infant, Newborn , Lung Diseases, Interstitial/complications , Lung Diseases, Interstitial/diagnosis , Male
9.
BMJ Open Qual ; 10(1)2021 03.
Article in English | MEDLINE | ID: mdl-33707289

ABSTRACT

Poor nutritional status in children with cancer can impact treatment outcomes and mortality. Nutrition screening is a simple yet effective approach to identify malnutrition risk for early intervention. We aim to improve the identification of children with cancer at high risk of malnutrition, so that nutritional intervention and rehabilitation can commence early for these children. Our multidisciplinary team conducted a root cause analysis and concluded that the generic screening tool did not differentiate malnutrition risk for different cancer types, stage and intensity of treatment. Hence, a screening tool that considered the identified factors was tested for reliability and validity first. Subsequently, we used the Plan, Do, Study, Act model with two improvement cycles to put in place a systematic process to facilitate the implementation. The interventions included (1) instituting the tool in the electronic medical records and (2) direct referral to dietitian based on screening score.We compared pre- and post-implementation cohorts and demonstrated better identification of nutritionally at-risk patients (36.4%-85.7%, p<0.001) with the new tool as well as improved timeliness of nutritional intervention (3 days to 1 day from admission, p=0.010). A lower malnutrition rate (17.4%-6.5%, p<0.001) in the postimplementation cohort was also demonstrated. Nutritional intervention within 48 hours of admission led to an overall positive weight change at 3 months (+2.68%, IQR: -1.14 to 9.09 vs -0.43%, -6.60 to 2.29; p=0.036) in the malnourished patients from both cohorts. Further studies will be conducted to evaluate the scale of the effectiveness of early intervention and close nutritional monitoring, in improving the nutritional status of children with cancer. The collaborative partnership among the doctors, nurses and dietitians has helped to streamline and simplify nutrition screening, making it an efficient and sustainable system in our hospital.


Subject(s)
Neoplasms , Nutritional Status , Child , Early Detection of Cancer , Hospitals, Pediatric , Humans , Neoplasms/epidemiology , Nutrition Assessment , Reproducibility of Results , Singapore/epidemiology
10.
Front Pediatr ; 9: 639603, 2021.
Article in English | MEDLINE | ID: mdl-33614560

ABSTRACT

Background: Anthracyclines are widely used to treat childhood cancers; however, they cause cardiotoxicity. To address the paucity of clinical data from Asian populations, this study investigated the epidemiology of pediatric anthracycline-induced cardiotoxicity, during and after chemotherapy, in a multiethnic Asian population. Procedure: This was a single-center, retrospective analysis of 458 anthracycline-treated pediatric oncology patients at KK Women's and Children's Hospital, a tertiary children's hospital in Singapore from 2005 through 2015. We investigated cardiotoxicity (defined as left ventricular fractional shortening <28% on echocardiography) and its risk factors using univariate logistic regression as well as survival estimates through the Kaplan-Meier method to compare survival distribution between patients with and without cardiotoxicity. Results: Over a follow-up period of almost 4 years, we found that 7% (32/458) of the cohort developed cardiotoxicity, with 37.5% (12/32) of these manifesting as clinical heart failure, whilst the rest were asymptomatic. The cardiotoxic cohort demonstrated a significantly higher mortality rate compared to the non-cardiotoxic group at 46.9 vs. 19.2% (p < 0.001), of whom 3 (9.4%) died from end-stage heart failure. We found that traditional predictors such as female sex, age at diagnosis, and cumulative doxorubicin equivalent dose were not predictors of cardiotoxicity. Conclusion: Our study reaffirms that freedom from symptoms does not ensure normal heart function and suggests that children with abnormal ventricular systolic function have higher mortality risk compared to those with normal systolic function. The findings contribute to improved understanding of the Asian burden to aid development of measures to prevent or reduce the risk of cardiotoxicity.

11.
Blood Cells Mol Dis ; 88: 102547, 2021 05.
Article in English | MEDLINE | ID: mdl-33607590

ABSTRACT

INTRODUCTION: Transfusion-dependent thalassaemia is associated with complications related to iron overload from frequent red cell transfusions which affect quality of life. We collected data on the clinical outcomes, complications, socioeconomic status and health-related quality of life (HRQoL) of transfusion-dependent thalassaemia patients in Singapore, and analysed the associations between clinical and socioeconomic factors with development of transfusion-related complications and HRQoL scores. MATERIALS AND METHODS: This was a cross-sectional study of transfusion-dependent thalassaemia patients treated at four major public hospitals in Singapore. Clinical information was obtained from retrospective reviews of medical records. Socioeconomic data and patient-reported compliance to iron chelators were obtained from prospective interviews of patients or caregivers using a questionnaire. A validated, disease-specific HRQoL instrument, the TranQOL, was administered to patients and caregivers during a routine clinic or transfusion visit. RESULTS: Liver iron loading was the most common transfusion-related complication and occurred in 79% of patients. Cardiac iron loading was noted in 28.3% and endocrine complications were present in 34.2%. Liver iron loading was significantly associated with higher mean ferritin level. Cardiac iron loading was significantly associated with increasing age, higher mean ferritin level and type of iron chelator. Endocrine complications were associated with increasing age, higher mean ferritin level, type of iron chelator and poorer patient-reported compliance to iron chelators. The lowest TranQOL scores were reported by caregiver parents of patients aged less than 18 years. Lower TranQOL scores were significantly associated with increasing age, especially in the 31-50 age cohort, and with reception of social assistance. CONCLUSION: The main morbidities noted in transfusion-dependent thalassaemia patients in Singapore are from complications associated with iron loading. The cohort of older thalassaemia patients aged 31-50 experienced significantly higher rates of cardiac iron loading, endocrine complications and lower TranQOL scores compared to younger age cohorts.


Subject(s)
Blood Transfusion , Quality of Life , Thalassemia/therapy , Adolescent , Adult , Child , Child, Preschool , Cross-Sectional Studies , Female , Humans , Infant , Iron Chelating Agents/therapeutic use , Male , Middle Aged , Singapore/epidemiology , Socioeconomic Factors , Thalassemia/complications , Thalassemia/epidemiology , Transfusion Reaction , Young Adult
12.
Clin Lymphoma Myeloma Leuk ; 21(3): e290-e300, 2021 03.
Article in English | MEDLINE | ID: mdl-33384264

ABSTRACT

PURPOSE: To determine the prognostic factors in pediatric patients with acute myeloid leukemia (AML) and to assess whether their outcomes have improved over time. PATIENTS AND METHODS: Sixty-two patients with AML excluding acute promyelocytic leukemia were retrospectively analyzed. Patients in the earlier cohort (n = 36) were treated on the Medical Research Council (MRC) AML12 protocol, whereas those in the recent cohort (n = 26) were treated on the Malaysia-Singapore AML protocol (MASPORE 2006), which differed in terms of risk group stratification, cumulative anthracycline dose, and timing of hematopoietic stem-cell transplantation for high-risk patients. RESULTS: Significant improvements in 10-year overall survival and event-free survival were observed in patients treated with the recent MASPORE 2006 protocol compared to the earlier MRC AML12 protocol (overall survival: 88.0% ± 6.5% vs 50.1% ± 8.6%, P = .002; event-free survival: 72.1% ± 9.0 vs 50.1% ± 8.6%, P = .045). In univariate analysis, patients in the recent cohort had significantly lower intensive care unit admission rate (11.5% vs 47.2%, P = .005) and numerically lower relapse rate (26.9% vs 50.0%, P = .068) compared to the earlier cohort. Multivariate analysis showed that treatment protocol was the only independent predictive factor for overall survival (hazard ratio = 0.21; 95% confidence interval, 0.06-0.73, P = .014). CONCLUSION: Outcomes of pediatric AML patients have improved over time. The more recent MASPORE 2006 protocol led to significant improvement in long-term survival rates and reduction in intensive care unit admission rate.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Hematopoietic Stem Cell Transplantation , Leukemia, Myeloid, Acute/mortality , Leukemia, Myeloid, Acute/therapy , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Child, Preschool , Clinical Decision-Making , Combined Modality Therapy , Disease Management , Female , Humans , Induction Chemotherapy , Infant , Leukemia, Myeloid, Acute/diagnosis , Male , Prognosis , Retrospective Studies , Survival Analysis , Transplantation, Homologous , Treatment Outcome
13.
World J Pediatr Surg ; 4(4): e000303, 2021.
Article in English | MEDLINE | ID: mdl-36475241

ABSTRACT

Background: Diagnostic biopsies of pediatric anterior mediastinal masses (AMMs) are high-risk procedures in which general anesthesia (GA) is traditionally avoided. However, awareness of historically recognized risk factors and corresponding perioperative management have improved over time and may now no longer strictly preclude the use of GA. Therefore, in this study, we examined the association of anesthetic and surgical risk factors and modalities with resulting procedural and survival outcomes in a current patient cohort. Methods: We retrospectively reviewed charts of 35 children with AMMs who underwent initial diagnostic biopsies between January 2001 and August 2019, and determined tracheal compression and deviation from archival CT scans and procedural and disease outcomes. Results: Twenty-three (65%) patients underwent GA while 12 (35%) received sedation. Among patients with available CT measurements, 13 of 25 (52%) had >50% anteroposterior tracheal diameter reduction. Patients with >50% anteroposterior tracheal compression received sedation more frequently (p=0.047) and were positioned upright (p=0.015) compared with patients with ≤50% compression, although 4 of 13 and 9 of 12, respectively, still received GA. Intraoperative adverse events (AEs) occurred in four (11.4%) patients: three received GA, and all were positioned supine or lateral. AEs were not associated with radiographic airway risk factors but were significantly associated with morphine and sevoflurane use (p<0.001) and with thoracoscopic biopsies (p=0.035). There were no on-table mortalities, but four delayed deaths occurred (three related to disease and one from late procedural complications). Conclusions: In a current cohort of pediatric AMM biopsies, patients with >50% anteroposterior tracheal compression were more frequently managed with a conservative perioperative management strategy, though not completely excluding GA. The corresponding reduction in frequency of procedural AEs in this traditionally high-risk group suggests that increased awareness of procedural risk factors and appropriate risk-guided perioperative management choices may obviate the procedural mortality historically associated with pediatric AMM biopsies.

14.
Cancer Sci ; 111(10): 3780-3792, 2020 Oct.
Article in English | MEDLINE | ID: mdl-32777141

ABSTRACT

Ex vivo evaluation of personalized models can facilitate individualized treatment selection for patients, and advance the discovery of novel therapeutic options. However, for embryonal malignancies, representative primary cultures have been difficult to establish. We developed patient-derived cell cultures (PDCs) from chemo-naïve and post-treatment neuroblastoma tumors in a consistent and efficient manner, and characterized their in vitro growth dynamics, histomorphology, gene expression, and functional chemo-response. From 34 neuroblastoma tumors, 22 engrafted in vitro to generate 31 individual PDC lines, with higher engraftment seen with metastatic tumors. PDCs displayed characteristic immunohistochemical staining patterns of PHOX2B, TH, and GD2 synthase. Concordance of MYCN amplification, 1p and 11q deletion between PDCs and patient tumors was 83.3%, 72.7%, and 80.0% respectively. PDCs displayed a predominantly mesenchymal-type gene expression signature and showed upregulation of pro-angiogenic factors that were similarly enriched in culture medium and paired patient serum samples. When tested with standard-of-care cytotoxics at human Cmax -equivalent concentrations, MYCN-amplified and non-MYCN-amplified PDCs showed a differential response to cyclophosphamide and topotecan, which mirrored the corresponding patients' responses, and correlated with gene signatures of chemosensitivity. In this translational proof-of-concept study, early-phase neuroblastoma PDCs enriched for the mesenchymal cell subpopulation recapitulated the individual molecular and phenotypic profile of patient tumors, and highlighted their potential as a platform for individualized ex vivo drug-response testing.


Subject(s)
Homeodomain Proteins/genetics , N-Myc Proto-Oncogene Protein/genetics , Neuroblastoma/drug therapy , Transcription Factors/genetics , Tyrosine 3-Monooxygenase/genetics , Animals , Antineoplastic Agents/pharmacology , Cell Line, Tumor , Cyclophosphamide/pharmacology , Gene Expression Regulation, Neoplastic/drug effects , Heterografts , Humans , Mice , N-Acetylgalactosaminyltransferases/genetics , Neuroblastoma/genetics , Neuroblastoma/pathology , Precision Medicine , Topotecan/pharmacology , Transcriptome/genetics
15.
Pediatr Blood Cancer ; 67(6): e28242, 2020 06.
Article in English | MEDLINE | ID: mdl-32187445

ABSTRACT

OBJECTIVE: Pediatric oncology patients admitted to the pediatric intensive care unit (PICU) are at high risk of mortality. This study aims to describe the epidemiology of and the risk factors for mortality in these patients. STUDY DESIGN: This is a retrospective cohort study including all consecutive PICU oncology admissions from 2011 to 2017. Demographic and clinical risk factors between survivors and nonsurvivors were compared. Both univariate and multivariate Cox proportional hazard regression models were used to quantify the association between 60-day mortality and admission categories, accounting for other covariates (Pediatric Risk Of Mortality [PRISM] III score and previous bacteremia). MAIN OUTCOME MEASURES: The primary outcome was 60-day mortality. RESULTS: The median (interquartile range) age and PRISM III scores of pediatric oncology patients admitted to the PICU were 7 (3, 12) years and 3 (0, 5), respectively. The most common underlying oncological diagnoses were brain tumors (73/200 [36.5%]) and acute lymphoblastic leukemia (36/200 [18.0%]). Emergency admissions accounted for approximately half of all admissions (108/200 [54.0%]), including cardiovascular (24/108 [22.2%]), neurology (24/108 [22.2%]), respiratory (22/108 [20.4%]), and "other" indications (38/108 [35.2%]). The overall 60-day mortality was 35 of 200 (17.5%). Independent risk factors for mortality were emergency respiratory and neurology categories of admission (adjusted hazard ratio[aHR]: 5.62, 95% confidence interval [95% CI]: 1.57, 20.19; P = .008 and aHR: 6.96, 95% CI: 2.04, 23.75; P = .002, respectively) and previous bacteremia (aHR: 3.37, 95% CI: 1.57, 7.20; P = .002). CONCLUSION: Emergency respiratory and neurology admissions and previous bacteremia were independent risk factors for 60-day mortality for pediatric oncological patients admitted to the PICU.


Subject(s)
Cardiovascular Diseases/mortality , Hospital Mortality/trends , Intensive Care Units, Pediatric/statistics & numerical data , Neoplasms/mortality , Nervous System Diseases/mortality , Respiratory Distress Syndrome/mortality , Severity of Illness Index , Adolescent , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/etiology , Child , Child, Preschool , Female , Follow-Up Studies , Humans , Incidence , Infant , Infant, Newborn , Male , Neoplasms/complications , Nervous System Diseases/epidemiology , Nervous System Diseases/etiology , Outcome Assessment, Health Care , Prognosis , Respiratory Distress Syndrome/epidemiology , Respiratory Distress Syndrome/etiology , Retrospective Studies , Risk Factors , Singapore/epidemiology , Survival Rate
16.
J Paediatr Child Health ; 56(1): 123-129, 2020 Jan.
Article in English | MEDLINE | ID: mdl-31145505

ABSTRACT

AIM: Central line-associated bloodstream infection associated bloodstream infection (CLABSI) is a serious complication of patients on central venous catheters (CVC). Taurolidine-citrate solution (TCS) is a catheter-lock solution with broad-spectrum antimicrobial action. This study's aim was to evaluate the efficacy of TCS in reducing CLABSI rates in paediatric haematology-oncology (H/O) and gastrointestinal (GI) patients with long-term CVC. METHODS: This was an open-label trial of H/O and GI inpatients with the following inclusion criteria: <17 years old, more than or equal to one previous CLABSI and a minimum TCS dwell time of ≥8 h. CLABSI per 1000 catheter-days was calculated from each patient's first CVC insertion till 14 December 2017 or until TCS discontinuation. RESULTS: Thirty-three patients were recruited with a median age of 3.5 years; H/O and GI constituted 60.6 and 39.4% respectively. CVC types were Hickman line (45.5%), implantable port (24.2%) and peripherally inserted central catheter (30.3%). Mean pre- and post-TCS CLABSI rates per 1000 catheter-days were 14.44 and 2.45 (P < 0.001) for all patients; 16.55 and 2.81 for H/O patients; and 11.21 and 1.90 for GI patients, respectively. Pre- and post-TCS rate ratio was 0.20, 0.10 and 0.30 for all, H/O and GI patients, respectively (P < 0.001). TCS also led to a reduction in CVC removal from 66.7 to 9.09% (P < 0.001). CONCLUSIONS: TCS usage was highly successful in CLABSI reduction by 80% in all patients, 90% in H/O and 70% in GI patients. In patients with high baseline CLABSI rates, TCS is an effective catheter-lock therapy to reduce CLABSI rates in paediatric patients.


Subject(s)
Bacteremia , Catheter-Related Infections , Catheterization, Central Venous , Central Venous Catheters , Hematology , Adolescent , Catheter-Related Infections/epidemiology , Catheter-Related Infections/prevention & control , Catheterization, Central Venous/adverse effects , Central Venous Catheters/adverse effects , Child , Child, Preschool , Citrates , Citric Acid , Humans , Taurine/analogs & derivatives , Thiadiazines
17.
Int J Cancer ; 144(6): 1234-1242, 2019 03 15.
Article in English | MEDLINE | ID: mdl-30362502

ABSTRACT

Wilms tumor demonstrates significant interethnic epidemiological, histological and outcome differences, and is rare and poorly studied among Asians. We compared the clinicopathological, and loss of heterozygosity (LOH) profile and survival outcomes of Asian and non-Asian patients with Wilms tumor. Clinical charts and histological slides from patients with malignant renal tumors over a period of 20 years were retrospectively reviewed. We adapted a genotyping assay to determine 1p36 and 16q21-22 LOH in formalin-fixed paraffin-embedded (FFPE) specimens, and compared these characteristics between Asian and non-Asian patients. Fifty-three (79.1%) Asian and 14 (20.9%) non-Asian patients had Wilms tumors. Compared to non-Asians, Asians were younger (mean 4.6 and 4.0 years, respectively), had more equal gender distribution (female: male = 1.8 and 1.0, respectively), fewer tumors with unfavorable histology (25.0% and 4.1%, respectively, p = 0.05), and less advanced disease at presentation, yet similar nodal metastases rates (16.7% and 18.4%, respectively). No Asian patients had bilateral tumors. Our adapted genotyping assay accurately determined LOH in FFPE specimens <10 years post-fixation. Among 30 Asian patients, 1p and 16q LOH were each detected in 5 (16.7%) patients, respectively-similar to rates reported in other ethnicities. Yet after similar treatment with National Wilms Tumor Study regimens, 15-year event-free and overall survival for Asian patients was 95.7% and 96.3% respectively. In summary, despite similar nodal metastasis and LOH rates, Asian patients had fewer unfavorable histology tumors, lower-stage disease, and better survival outcomes. The bases for these differences and implications on treatment strategy for these patients warrant further study.


Subject(s)
Asian People/genetics , Kidney Neoplasms/genetics , Loss of Heterozygosity , Wilms Tumor/genetics , Age Factors , Child , Child, Preschool , Chromosomes, Human, Pair 1/genetics , Chromosomes, Human, Pair 11/genetics , Chromosomes, Human, Pair 16/genetics , Female , Humans , Infant , Kidney Neoplasms/mortality , Kidney Neoplasms/pathology , Male , Neoplasm Staging , Progression-Free Survival , Retrospective Studies , Singapore/epidemiology , Survival Analysis , Wilms Tumor/mortality , Wilms Tumor/pathology
18.
NPJ Genom Med ; 3: 30, 2018.
Article in English | MEDLINE | ID: mdl-30455982

ABSTRACT

Assessment of cancer predisposition syndromes (CPS) in childhood tumours is challenging to paediatric oncologists due to inconsistent recognizable clinical phenotypes and family histories, especially in cohorts with unknown prevalence of germline mutations. Screening checklists were developed to facilitate CPS detection in paediatric patients; however, their clinical value have yet been validated. Our study aims to assess the utility of clinical screening checklists validated by genetic sequencing in an Asian cohort of childhood tumours. We evaluated 102 patients under age 18 years recruited over a period of 31 months. Patient records were reviewed against two published checklists and germline mutations in 100 cancer-associated genes were profiled through a combination of whole-exome sequencing and multiplex ligation-dependent probe amplification on blood-derived genomic DNA. Pathogenic germline mutations were identified in ten (10%) patients across six known cancer predisposition genes: TP53, DICER1, NF1, FH, SDHD and VHL. Fifty-four (53%) patients screened positive on both checklists, including all ten pathogenic germline carriers. TP53 was most frequently mutated, affecting five children with adrenocortical carcinoma, sarcomas and diffuse astrocytoma. Disparity in prevalence of germline mutations across tumour types suggested variable genetic susceptibility and implied potential contribution of novel susceptibility genes. Only five (50%) children with pathogenic germline mutations had a family history of cancer. We conclude that CPS screening checklists are adequately sensitive to detect at-risk children and are relevant for clinical application. In addition, our study showed that 10% of Asian paediatric solid tumours have a heritable component, consistent with other populations.

19.
Arch Dis Child ; 103(6): 578, 2018 06.
Article in English | MEDLINE | ID: mdl-28874367
20.
J Pediatr Hematol Oncol ; 39(6): e303-e306, 2017 08.
Article in English | MEDLINE | ID: mdl-28697170

ABSTRACT

Children with hemophagocytic lymphohistiocytosis (HLH) are at an increased risk of critical illness. In this study, we described the clinical characteristics of critically ill children with HLH and identify factors associated with poor clinical outcomes. Children who were diagnosed with HLH with emergent admission to Children's Intensive Care Unit (CICU) between January 1, 2000 and October 31, 2015 were included. The primary outcome was CICU mortality. Over the 15-year period, there were 14 critically ill patients with HLH with 23 CICU admissions. Median age at HLH diagnosis was 8.2 years (interquartile range [IQR], 2.9 to 11.3). Overall CICU mortality was 8 of 23 CICU admissions (34.8%). Factors that were associated with CICU mortality in critically ill children with HLH identified in this study include: a worse median pediatric index of mortality 2 score (4.7% in survivors [IQR, 2.9% to 11.6%] vs. 2.4% [IQR, 1.2% to 4.3%]; P=0.031); higher median peak serum lactate level (mmol/L) within 24 hours of admission (5.6 [IQR, 2.7 to 17.4] vs. 1.6 [IQR, 1.2 to 2.8]; P=0.032); the need for mechanical ventilation (100% vs. 46.7%; P=0.019); inotropic support (87.5% vs. 20.0%; P=0.006); renal replacement therapy (50% vs. 0%; P=0.008); and blood product transfusion episodes (24.5 [IQR, 14.3 to 46.8] vs. 3.0 [IQR, 1.0 to 9.0]; P=0.002). Further studies are required to validate the factors that are associated with poor outcomes in critically ill children with HLH.


Subject(s)
Intensive Care Units, Pediatric , Lymphohistiocytosis, Hemophagocytic/therapy , Blood Transfusion/statistics & numerical data , Child , Child, Preschool , Critical Illness , Hospitalization , Humans , Lymphohistiocytosis, Hemophagocytic/mortality , Renal Replacement Therapy/statistics & numerical data , Respiration, Artificial/statistics & numerical data
SELECTION OF CITATIONS
SEARCH DETAIL
...