Search

Fatigue is an overlooked symptom for musculoskeletal diseases, including rare conditions like systemic sclerosis (SSc). The purpose of this study were the following: (1) to adapt the content and delivery method of an existing fatigue intervention, and (2) to determine the feasibility of Fatigue and Activity Management Education in Systemic Sclerosis (FAME-iSS).In Phase 1 adaptations were recorded using the Framework for Modification and Adaptations. In Phase 2, participants completed the 6-week FAME-iSS intervention and baseline, post-intervention, and 3-month follow-up assessments measuring fatigue levels, fatigue impact, mental health, self-efficacy, and use of energy conservation strategies. Qualitative data included a post-intervention focus group and 3-month follow-up interviews.Three main changes were made to the original intervention: (1) the content was adapted from management of Lupus-related fatigue to management of SSc-related fatigue, (2) context for delivery from Ireland to United States, and (3) in-person to online format. Participants (n = 4) were 51.8 ± 12.1 years old, had been diagnosed with SSc for 12.0 ± 8.0 years, were receiving disability support, and had college degrees. All participants had 100% attendance and completed all study activities. Participants had positive comments about the programme format, content, and implementation. Post-intervention, improvements were observed in most measures. Moderate effect sizes were noted in fatigue and self-efficacy scores.Participants' positive responses supported the need for FAME-iSS for people with SSc. Even with the small sample, FAME-iSS led to improvements in fatigue and use of energy conservation strategies. The online format allowed for participation and sharing of ideas, especially during the global pandemic.

Background: Childhood cancer, although rare, remains an important cause of death worldwide. The outcomes of children with all cancer types in South Africa are not well-documented. Aim: The aim of the article was to determine local childhood cancer survival rates and establish determinants of survival. Setting: The study was conducted at a state and a private hospital in South Africa. Methods: This retrospective cohort study consecutively included all children with a proven malignancy from 01 January 2012 to 31 December 2016. Univariable and multivariable analyses were used to establish which factors significantly impacted overall survival (OS). Results: Of a total of 677 study participants, 71% were black South Africans. The estimated 5-year overall survival (OS) was 57% (95% confidence interval [CI]: 53-61%) and significant determinants of OS on the multivariable analysis included: ethnicity, cancer-type and nutritional status. White and Indian patients had higher OS compared to black patients (hazard ration [HR] (95% CI) 0.46 (0.30-0.69) p = 0.0002 and HR (95%) 0.38 (0.19-0.78) p = 0.0087, respectively). Underweight patients had inferior survival (HR (95% CI) 1.78 (1.28-2.47)) p = 0.0006. Patients with neuroblastoma had an increased risk of dying compared to those with leukaemia (HR [95% CI] 1.78 [1.08-2.94]) p = 0.025. Progression of disease was the most common cause of death, followed by disease relapse. Conclusion: The childhood cancer survival rate obtained in this study can be used as a baseline to facilitate improvement. Non-modifiable prognostic factors included ethnicity and cancer-type whilst modifiable risk factors included undernutrition. Undernutrition should be addressed on a national and local level to improve survival.

Aims: Image-defined risk factors (IDRFs) in neuroblastoma predict surgical complications and management outcomes. As there is a lack of data regarding the association of IDRFs with clinical and pathological factors, this study evaluated the prognostic value of IDRFs to predict neuroblastoma survival outcomes. Materials and methods: This was a retrospective study including 345 patients and reviewed diagnostic imaging for 20 IDRFs, pleural effusions and ascites. The IDRFs were grouped into five `primary IDRFs' cohorts with vascular encasement, involvement of multiple body compartments, organ infiltration, airway obstruction and intraspinal extension. The association between clinical, histopathological and biological characteristics of neuroblastoma and management was evaluated. Results: More patients without IDRFs had operations compared with patients with IDRFs, with a trend towards significance (64.4% versus 35.6%, P = 0.082). Patients with multiple compartment tumour involvement (P = 0.003) and organ infiltration (P < 0.001) had a higher risk of surgical complications. The 5-year overall survival of the group with more than one IDRF was 0.0% and those with pleural effusions or ascites 6.7%, associated with the worst outcome (P = 0.005). The total number of IDRFs was not predictive of the metastatic remission rate (P = 0.585) or overall survival (P = 0.142), with no conclusive association found between IDRF groups and clinical or biological markers. Conclusions: Patients with more than one IDRF had the shortest survival time, whereas those with pleural effusions and ascites at diagnosis had a poor outcome. Standardised reporting of IDRFs is crucial for predicting prognosis. (C) 2021 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Background. Nephroblastoma is the most common paediatric renal malignancy, affecting 1 in 10 000 children worldwide. Between 5% and 10% present bilaterally. Objective. To review two centre’s experience of bilateral Wilms’ tumour in order to improve future management practices. Methods. This was a retrospective case review of nephroblastomas treated at the Chris Hani Baragwanath and Charlotte Maxeke academic hospitals from 1 January 2003 to 31 December 2013. Results. Eighteen patients (8.04%) presented with bilateral disease and were younger than those with unilateral disease. Three patients presented with metachronous disease at a median age of 23 months; initial presentation was at a median age of 2 months. The remaining 15 patients presented with synchronous disease at a median age of 27 months. Treatment followed aspects of the SIOP 9 protocol. Two patients died before surgery. Thirteen kidneys were removed. Twelve patients underwent nephron-sparing surgery, with microscopically positive resection margins seen in six kidneys post surgery. Two patients with residual microscopic disease relapsed. Three kidneys demonstrated unfavourable histology. Nephroblastomatosis was identified in one kidney. Eight patients were alive and disease free and three were alive with disease. An overall and disease-free survival rate of 66.67% and 55.56%, respectively, was found for this cohort. Neither age >2 years nor metachronous disease was associated with a poorer prognosis. Conclusion. Bilateral nephroblastoma is a complex disease. The majority of patients in this series presented with advanced local disease. Relapse was more commonly influenced by the presence of microscopically positive margins than metastatic disease at presentation.

Purpose The aim of the World Health Organization-International Paediatric Oncology Society is to improve childhood cancer survival in low- and middle-income countries to 60% by 2030. This can be achieved using standardised evidence-based national treatment protocols for common childhood cancers. The aim of the study was to describe the development and implementation of the SACCSG NB-2017 neuroblastoma (NB) treatment protocol as part of the treatment harmonisation process of the South African Children’s Cancer Study Group. Methods The Consolidated Framework for Implementation Research was used to identify factors that could influence the implementation of the national NB protocol as a health care intervention. The evaluation was done according to five interactive domains for implementation: intervention characteristics, inner setting, outer setting, individual or team characteristics and the implementation process. Results The protocol was developed over 26 months by 26 physicians involved in childhood cancer management. The process included an organisational phase, a resource identification phase, a development phase and a research ethics approval phase. Challenges included nationalised inertia, variable research ethical approval procedures with delays and uncoordinated clinical trial implementation. Conclusion The implementation of the national NB protocol demonstrated the complexity of the implementation of a national childhood cancer treatment protocol. However, standardised paediatric cancer treatment protocols based on local expertise and resources in limited settings are feasible. Supplementary Information The online version contains supplementary material available at 10.1007/s10552-021-01424-2.

Background Fanconi anemia (FA) is phenotypically diverse, hereditary condition associated with bone marrow failure, multiple physical abnormalities, and an increased susceptibility to the development of malignancies. Less recognized manifestations of FA include endocrine abnormalities. International discourse has highlighted that these abnormalities are widespread among children and adults with FA. To date there has been no systematic study that has evaluated the endocrine abnormalities in a cohort of patients with FA, homozygous for a founder mutation (c.637_643del (p.Tyr213Lysfs*6)) in FANCG. The objectives of the study were to evaluate endocrine gland function in patients with FA of a single FA genotype, and to determine the frequency and nature of endocrine abnormalities in this group. Methods Cross‐sectional, descriptive study of 24 South African patients of African ancestry with FA (homozygous for a FANCG founder mutation). Outcomes measured included growth, pubertal status, growth hormone axis screening, thyroid gland function, glucose and insulin metabolism and bone age (BA). Results Endocrine dysfunction was present in 70.8% (17 of 24), including abnormal insulin‐like growth factor 1 (IGF‐1)/insulin‐like growth factor‐binding protein 3 (IGFBP‐3) in 25.0% (6 of 24), insulin resistance in 41.7% (10 of 24), abnormal thyroid function in 16.7% (4 of 24) and short stature in 45.8% (11 of 24). No abnormalities of glucose metabolism were identified. Abnormal pubertal status was seen in three males (12.5%). Abnormal BAs were present in 34.8% (8 of 23). Conclusion Endocrine abnormalities occur at a high frequency in patients with FA, homozygous for a FANCG founder mutation, similar to other FA cohorts. Our data are specific to FA patients with a single genotype, and therefore provide the first genotype‐phenotype information on endocrine abnormalities in South African patients, homozygous for a FANCG founder mutation. Recommendations regarding endocrine screening in this patient subgroup are made, including, but not limited to, baseline testing of thyroid function, fasted insulin and glucose, and IGF‐1 and IGFBP‐3., Endocrine abnormalities are a lesser known complication of Fanconi anemia. Endocrine abnormalities occur at a high frequency in South African patients with Fanconi anemia, homozygous for a FANCG founder mutation.

Purpose Low- and middle-income countries (LMICs) reported a higher median age at diagnosis of neuroblastoma (NB) compared to high-income countries. The aim was to determine if the optimal age at diagnosis, which maximizes the difference in overall survival between younger versus older patients in the South African population was similar to the internationally validated 18 months age cut-point. Methods Four hundred sixty NB patients diagnosed between 2000 and 2016 were included. Receiver operating characteristic (ROC) curves were used to predict potential age cut-point values for overall survival in all risk group classifications. Risk ratios, sensitivity, specificity, and positive and negative predictive values at the specific cut-points were estimated with 95% confidence intervals, and time to mortality by age at the specific cut-points was shown with Kaplan-Meier curves and compared using log-rank tests. Results The median age at diagnosis for the total cohort was 31.9 months (range 0.2-204.7). For high-risk (HR), intermediate-risk, low-risk, and very low-risk patients, the median age at diagnosis was, respectively, 36 months (range 0.4-204.7), 16.8 months (range 0.7-145.1), 14.2 months (range 2.0-143.5), and 8.7 months (range 0.2-75.6). The ROC curves for the total NB cohort (area under the curve [AUC] 0.696; P < .001) and HR (AUC 0.682; P < .001) were analyzed further. The optimal cut-point value for the total cohort was at 19.1 months (sensitivity 59%; specificity 78%). The HR cohort had potential cut-point values identified at 18.4 months age at diagnosis (sensitivity 45%; specificity 87%) and 31.1 months (sensitivity 67%; specificity 62%). The 19.1 months cut-point value in the total cohort and the 18.4 months cut-point value in HR were as useful in predicting overall survival as 18 months age at diagnosis. Conclusion The 18 months cut-point value appears to be the appropriate age for prognostic determination, despite the higher median age at diagnosis in South Africa.

Fanconi Anaemia (FA) is an autosomal recessive disorder characterised by defects in DNA repair, associated with chromosomal instability and cellular hypersensitivity to DNA cross-linking agents such as mitomycin C (MMC). The FA repair pathway involves complex DNA repair mechanisms crucial for genomic stability. Deficiencies in DNA repair genes give rise to chromosomal radiosensitivity. FA patients have shown increased clinical radiosensitivity by exhibiting adverse normal tissue side-effects. The study aimed to investigate chromosomal radiosensitivity of homozygous and heterozygous carriers of FA mutations using three micronucleus (MN) assays. The G0 and S/G2MN assays are cytogenetic assays to evaluate DNA damage induced by ionising radiation in different phases of the cell cycle. The MMC MN assay detects DNA damage induced by a crosslinking agent in the G0 phase. Patients with a clinical diagnosis of FA and their parents were screened for the complete coding region of 20 FA genes. Blood samples of all FA patients and parents were exposed to ionising radiation of 2 and 4Gy. Chromosomal radiosensitivity was evaluated in the G0 and S/G2 phase. Most of our patients were homozygous for the founder mutation FANCG c.637_643delTACCGCC; p.(Tyr213Lysfs*6) while one patient was compound heterozygous for FANCG c.637_643delTACCGCC and FANCG c.1379G > A, p.(Gly460Asp), a novel missense mutation. Another patient was compound heterozygous for two deleterious FANCA mutations. In FA patients, the G0- and S/G2-MN assays show significantly increased chromosomal radiosensitivity and genomic instability. Moreover, chromosomal damage was significantly elevated in MMC treated FA cells. We also observed an increase in chromosomal radiosensitivity and genomic instability in the parents using 3 assays. The effect was significant using the MMC MN assay. The MMC MN assay is advantageous as it is less labour intense, time effective and has potential as a reliable alternative method for detecting FA patients from parents and controls.

Aim: This paper presents a 20-year review of retinoblastoma in Johannesburg, South Africa, aiming to better characterize the disease in this sub-Saharan setting. Methods: The study represents a retrospective case series of retinoblastoma patients presenting to Charlotte Maxeke Johannesburg Academic Hospital and Chris Hani Baragwanath Academic Hospital between January 1, 1992, and December 31, 2011. Results: The total number of cases identified was 282, with 245 meeting the study inclusion criteria. Retinoblastoma comprised 6.9% of the total pediatric oncology presentations; 65.3% were unilateral, 34.3% bilateral, and 0.4% trilateral. The overall male-to-female ratio was 1.08. The mean age at presentation overall was 32.6 months (median 28.0), in the unilateral group 39.4 months (median 33.0), and in the bilateral group 19.7 months (median 17.0). The mean delay to presentation overall was 7.0 months (median 4.0). The most frequent presenting symptoms were leukocoria (37.1%) and proptosis (34.7%). The distribution of disease stages at presentation (International Retinoblastoma Staging System) was 1.6% stage 0, 24.1% stage I, 27.8% stage II, 16.3% stage III, and 25.3% stage IV. 26.5% defaulted care. The 5-year Kaplan-Meier survival estimate was 57.7% overall. Conclusion: This study shows that delayed presentation and refusal of therapy remains a significant barrier to effective treatment in this African setting.

Janet PooleCh’oe, In-ho. Another Man’s City. Translated by Bruce and Ju-Chan Fulton. Champaign: Dalkey Archive Press, 2014. 190 pp.Choi, In-hun. The Square. Translated by Kim Seong-kon. Champaign: ...

Background Clinical manifestations of renal dysfunction in childhood cancer survivors include hypertension, proteinuria, tubulopathy (and its biochemical consequences) and renal insufficiency. This study aimed to determine the factors associated with renal dysfunction in paediatric cancer survivors at a single centre in Johannesburg. Procedure A descriptive cross-sectional study was performed on 130 cancer survivors between 2 and 18 years of age. Physical examination and screening urine dipstick were performed on all patients. Blood results of samples routinely drawn were analysed. Results After a median follow-up period of 2 years, the various manifestations of renal dysfunction included decreased estimated glomerular filtration rate (eGFR), hypomagnesaemia, hypophosphataemia, proteinuria, haematuria and hypertension. In total, 34 survivors (26.15%) had at least one manifestation of renal dysfunction after completing treatment. The most prevalent manifestation of renal dysfunction was decreased eGFR (17.7%) followed by hypomagnesaemia (6.2%) and hypophosphataemia (4.6%). Patients with pre-existing renal dysfunction were three times more likely to have renal dysfunction post-treatment (P = 0.020). Ifosfamide (P = 0.010) and nephrectomy (P = 0.003) had independent significant impact on reduction in eGFR. High cumulative ifosfamide doses were identified as a possible cause for hypophosphataemia (P = 0.021). Conclusion While not clinically evident in the early follow-up period, the high rate of renal dysfunction is concerning. We suggest that patients with pre-existing renal dysfunction should be assessed by a nephrologist prior to initiation of cancer therapy, and nephro-protective measures should be employed stringently in all children with cancer. Patients with decreased eGFR should be followed up closely in a multidisciplinary late effects clinic.

Meeting the needs of people with co-existing mental health and addiction problems is a challenge faced by many mental health and addiction services and providers. A compounding factor has been the separation of mental health and addiction services which has meant that many people with co-existing mental health and addiction problems have fallen through the cracks between services or had issues not recognized or responded to, leading to poor health outcomes. This chapter describes the approach taken by New Zealand's workforce development centers to support services to improve responsiveness and workforce capability to work with people with co-existing mental health and addiction problems. International research on implementation is briefly summarized before discussion about the impact of the national approach and the barriers to implementation that have emerged. Recommendations for next steps conclude this chapter.

Background: The increasing intensity of treatment of paediatric malignancies has led to improved survival rates, but often necessitates intensive supportive care. The decision to admit a child to the paediatric intensive care unit (PICU) is based on the probability of both short-term and long-term survival in the context of severe resource constraints. Resource constraints in South Africa result in limited access of children with cancer to PICU facilities.Objectives: The aim of this study was to determine whether referrals by paediatric oncologists to a PICU in Johannesburg were appropriate by analysing indications for admission, underlying diagnoses, duration and costs of admissions, and overall outcomes.Methods: A retrospective review of consecutive PICU admissions over a 12-year period was performed. Data from all patients with histologically proven malignant conditions were included and analysed using descriptive statistical methods, Kaplan–Meier curves, log-rank analysis and Fisher’s exact test.Results: There were 5704 recorded admissions to PICU in the study period. Of these admissions, 120 (2.1%) were for patients with malignancies. The majority of PICU oncology admissions were for post-operative care, and the median duration of stay was 1 day (interquartile range: 1–3 days). The short-term mortality rate of oncology patients in PICU was 13.3% in comparison with 16.2% in the overall PICU population. The 4-year overall survival rate post PICU discharge was 54%.Conclusion: The documented short-term mortality rate indicates that referrals by paediatric oncologists are consistent with current PICU admission policies. Oncologists should assess the prognosis for survival before requesting admission to PICU, and, resources permitting, these patients should be accepted to PICU.

This article attempts to rethink the question of modernism in colonial Korea by proposing a move away from formalist definitions of modernism and toward an understanding of modernism as an affirmation of modernity as a culture of time. This approach attempts to free Korean literary texts from the burden of being read as formal repetitions of European literary forms and instead allows the Korean texts to testify to the workings of their own temporalization. After laying out the theoretical and material grounds for late colonial modernism, the article provides a reading of two works that suggest decadence as an important mode through which the contradictions of the late colonial era could be thought and represented. As an aesthetic conveying a sense of an ending, decadence allowed for a confrontation with the problem of historical transformation just as the colonial government announced wartime mobilization policies that attempted to write a new future for Korea and Koreans.

In neonates presenting with a non-immune haemolytic anaemia, a high index of suspicion is raised for hereditary red cell membrane disorders. The distinction between red cell membrane disorders, however, is often difficult in neonates in the absence of a complete family history. We describe a case of a 26-day-old female twin who presented with jaundice and severe haemolysis, which required multiple red cell transfusions. Laboratory investigations revealed a non-immune haemolysis. Red cell membrane extraction and sodium dodecyl sulphate-polyacrylamide gel electrophoresis analysis, including spectrin analysis, revealed the presence of mutant spectrin αI/74. A diagnosis of hereditary elliptocytosis with transient infantile poikilocytosis was favoured. On follow-up at 4 months, a decline in haemolysis was observed.

Malignant liver tumors (mostly hepatoblastoma [HB] and hepatocellular carcinoma [HCC]) are uncommon, representing 0.5%–2% of childhood malignancies worldwide. The pattern of liver tumors appears to differ in Southern Africa as a result of infectious factors (e.g., hepatitis B/retroviral disease (HIV). This study aimed to assess recent changes in the prevalence and surgical management of liver tumors in South African children. Data were obtained from the tumor registry and pediatric oncology units in South African hospitals to audit and review the epidemiology, treatment, and outcome of malignant hepatic tumors in South African children. Malignant primary hepatic tumors were reported in 274 children (ages 0–14 years) from 1988 through June 2006. Of these 134 (48%) had HB; 77 (27%) had HCC (9 [3%] fibrolamellar subtype); 38 (13%), vascular tumors; and 17 (6%), liver sarcomas. In a further 8 patients (3%) other tumors included lymphoma and endodermal sinus tumor. Vascular tumors included hemangioendotheliomas (12), and there were 5 malignant tumors in children with HIV, including 1 angiosarcoma and 13 Kaposi sarcoma-like tumors. Hepatoblastoma occurred at a mean age of 1.47 years, and none were encountered in patients > 4 years of age. Hepatocellular carcinoma mostly occurred in the older patients (mean age: 10.48 years), but 6% presented in patients < 8 years of age (10 months, 2, 2.6, 5, 5, and 6 years). Hepatic sarcoma occurred at a mean age of 7.66 years and had a female predominance (M:F ratio: 0.4). The relative HCC prevalence (male predominant: hepatitis B related) was reflected in the low HB:HCC (1.67) ratio. However, a significant decrease in HCC was attributed to the effect of hepatitis B inoculation. There appeared to be an increase in the incidence of vascular tumors, presumably the result of an increase in Kaposi-like sarcoma in retrovirus-positive patients. The surgical resection rate was low because most patients presented late, with advanced disease. Survival was 11% and 52% for HB and HCC, respectively, and was related to chemotherapeutic response and complete surgical resection. Liver tumors appear to have a different epidemiological pattern in South Africa. The observed increased HCC prevalence appears to be decreasing with hepatitis B vaccination. Retroviral disease does not yet appear to have a major influence on the distribution of liver tumors in South Africa, although it possibly affects the vascular tumor prevalence.

BACKGROUND Little is known on the risk of cancer in HIV-positive children in sub-Saharan Africa. We examined incidence and risk factors of AIDS-defining and other cancers in pediatric antiretroviral therapy (ART) programs in South Africa. METHODS We linked the records of five ART programs in Johannesburg and Cape Town to those of pediatric oncology units, based on name and surname, date of birth, folder and civil identification numbers. We calculated incidence rates and obtained hazard ratios (HR) with 95% confidence intervals (CI) from Cox regression models including ART, sex, age, and degree of immunodeficiency. Missing CD4 counts and CD4% were multiply imputed. Immunodeficiency was defined according to World Health Organization 2005 criteria. RESULTS Data of 11,707 HIV-positive children were included in the analysis. During 29,348 person-years of follow-up 24 cancers were diagnosed, for an incidence rate of 82 per 100,000 person-years (95% CI 55-122). The most frequent cancers were Kaposi Sarcoma (34 per 100,000 person-years) and Non Hodgkin Lymphoma (31 per 100,000 person-years). The incidence of non AIDS-defining malignancies was 17 per 100,000. The risk of developing cancer was lower on ART (HR 0.29, 95%CI 0.09-0.86), and increased with age at enrolment (>10 versus

The spectrum of sickle cell disease (SCD) encompasses a heterogeneous group of disorders that include: (i) homozygous SCD (HbSS), also referred to as sickle cell anaemia; (ii) heterozygous SCD (HbAS), also referred to as sickle cell trait; and (iii) compound heterozygous states such as HbSC disease, HbSβ thalassaemia, etc. Homozygous or compound heterozygous SCD patients manifest with clinical disease of varying severity that is influenced by biological and environmental factors, whereas subjects with sickle cell trait are largely asymptomatic. SCD is characterised by vaso-occlusive episodes that result in tissue ischaemia and pain in the affected region. Repeated infarctive episodes cause organ damage and may eventually lead to organ failure. For effective management, regular follow-up with support from a multidisciplinary healthcare team is necessary. The chronic nature of the disease, the steady increase in patient numbers, and relapsing acute episodes have cost implications that are likely to impact on provincial and national health budgets. Limited resources mandate local management protocols for the purposes of consistency and standardisation, which could also facilitate sharing of resources between centres for maximal utility. These recommendations have been developed for the South African setting, and it is intended to update them regularly to meet new demands and challenges.

Fanconi anemia (FA) is a rare disorder of DNA repair, associated with various somatic abnormalities but characterized by hematological disease that manifests as bone marrow aplasia and malignancy. The mainstay of treatment, in developed nations, is hematopoietic stem cell transplantation (HSCT) with subsequent surveillance for solid organ and non-hematological malignancies. In South Africa, FA in the Black population is caused by a homozygous deletion mutation in the FANCG gene in more than 80% of cases. Many affected patients are not diagnosed until late in the disease course when severe cytopenia and bone marrow aplasia are already present. Most patients are not eligible for HSCT at this late stage of the disease, even when it is available in the state health care system. In this study, the hematological presentation and disease progression in 30 Black South African patients with FA, confirmed to have the FANCG founder mutation, were evaluated and compared to those described in other FA cohorts. Our results showed that patients, homozygous for the FANCG founder mutation, present with severe cytopenia but progress to bone marrow failure at similar ages to other individuals affected with FA of heterogeneous genotype. Further, the incidence of myelodysplastic syndrome is similar to that which has been previously described in other FA cohorts. Although severe cytopenia at presentation may be predicted by a higher number of somatic anomalies, the recognition of the physical FA phenotype in Black South African patients is challenging and may not be useful in expediting referral of suspected FA patients for tertiary level investigations and care. Given the late but severe hematological presentation of FA in Black South African patients, an investigative strategy is needed for earlier recognition of affected individuals to allow for possible HSCT and management of bone marrow disease.

BACKGROUND IN ADULTS: HIV increases the risk of certain cancers known or thought to have an underlying infectious etiology; the impact on the risk of cancer in children is less clear. METHODS: Here we report results of an on-going study at four pediatric oncology centers in South Africa in which children diagnosed with cancer are tested routinely for HIV. Odds ratios (OR) for the prevalence of various malignancies were calculated (with adjustment for age sex and center) for the children infected with HIV using all children with cancer and non-malignant conditions but not infected with HIV as a comparison group. RESULTS: Of 882 children with cancer 38 were HIV infected (for 12 the HIV status was unknown). HIV was associated with Kaposi sarcoma (all 10 cases were HIV infected; P < 0.001) and with Burkitt lymphoma (OR = 46.2 95% confidence interval (CI) 16.4-130.3; 13/33). For non-Burkitt non-Hodgkin lymphoma (NHL) 2/39 were HIV infected (OR = 5.0 95% CI 0.9-27.0). No other cancer type was significantly associated with HIV including lymphoid leukemias (OR = 0.4 95% CI 0.04-2.9; 1/172). CONCLUSIONS: Only Kaposi sarcoma and Burkitt lymphoma were significantly associated with HIV infection although results for non-Burkitt NHL were suggestive. Notably we did not identify an association between infection with HIV and lymphoid leukemias for which an underlying infectious etiology has been suggested. Copyright (c) 2010 Wiley-Liss Inc.

Background Granulocytic sarcomas (GS) have been associated with t(8;21). The prognosis of patients with GS is generally regarded as being less favorable than of patients with acute myeloblastic leukemia (AML). GS occurs relatively commonly in Africa and has been reported to affect 10–25% of black children presenting with AML. We sought to establish the incidence of GS in our pediatric population, to determine whether an association with t(8;21) existed, and to report on the outcome of these cases in a single series. Procedure. The records of consecutive pediatric patients treated for de novo AML in Johannesburg between January 1985–December 1995 were reviewed. Fifteen cases of GS among a total of 88 cases of AML presented to the Paediatric Haematology/Oncology Clinics of the Johannesburg and Baragwanath Hospitals. Fourteen (93%) of these patients were black male children. Results. All 9 cases of orbital GS (60%) and almost all cases with concurrent AML M2 had t(8;21). This translocation was present in only 4 (8.5%)of the remaining 47 AML cases without GS for which cytogenetic data were available. One case presented with a complex chromosomal translocation not previously associated with GS. The median disease-free survival of the GS patients, using conventional chemotherapy treatment protocols, was significantly better than for the patients with AML and no GS (P= 0.0004). Conclusions. Our data support a strong association between orbital GS, t(8;21), and AML M2 in the pediatric population. This entity occurred virtually exclusively in black male children at presentation. One third of these children who presented with AML had a GS. The favorable prognosis noted in our GS patients on standard induction and intensification therapy without local irradiation conflicts with some previous reports but is consistent with the favorable outcome documented in AML with t(8;21). Med. Pediatr. Oncol. 31: 144–149, 1998. © 1998 Wiley-Liss, Inc.

In 2008 the South African Children's Cancer Study Group decided to review the epidemiology, management, and chemotherapy response of HIV-positive children with malignancy.This is a retrospective analysis of data collected from the records of HIV-positive children diagnosed with malignancy at 7 university-based pediatric oncology units serving 8 of the 9 provinces in South Africa.Two hundred eighty-eight HIV-positive children were diagnosed with 289 malignancies between 1995 and 2009. Age at diagnosis ranged from 17 days to 18.64 years; median 5.79 years. Of the 220 HIV-associated malignancies, there were 97 Kaposi sarcomas, 61 Burkitt lymphomas, 47 other B-cell lymphomas including 2 primary central nervous system lymphomas, 12 Hodgkin lymphomas, and 3 leiomyosarcomas. Sixty-nine patients presented with non-AIDS-defining malignancies. More than 80% presented with advanced disease. Most patients (76.7%) were naive to antiretroviral therapy; 22.2% did not have access because it only became available in public hospitals in 2004. One hundred ninety-seven children were treated with curative intent; 91 received palliative care due to advanced malignancy and/or advanced HIV disease. Nearly one third had coexisting pathology, mostly tuberculosis. Overall survival for the whole group was 33.7%, but was 57.8% for those treated with antiretroviral therapy and chemotherapy.The study shows more Kaposi sarcoma and fewer primary central nervous system lymphomas among HIV-positive children than that is reported in the developed world, but confirms a higher incidence of non-Burkitt B-cell lymphoma than in HIV-negative children. The high number of non-AIDS-defining malignancies underscores the prevalence of HIV-AIDS in South Africa. The overall survival should improve with universal access to antiretrovirals and earlier diagnosis.

Haemoglobinopathies are a group of inherited disorders caused by structural variations of the haemoglobin molecule. We report the case of a 5-year-old girl suffering from chronic haemolytic anaemia. A diagnosis of compound heterozygous sickle cell disease (SCD) and β 0 -thalassaemia was established using haemoglobin sub-fractionation studies and parental screening. The latter revealed the father and mother to have heterozygous SCD and heterozygous β-thalassaemia, respectively. Evaluation of children with a haemolytic anaemia requires a thorough history and physical examination, appropriate laboratory testing and careful interpretation of the results.

Fanconi anemia is a genotypically and phenotypically heterogeneous condition, characterized microscopically by chromosomal instability and breakage. Affected individuals manifest growth restriction and congenital physical abnormalities; most progress to hematological disease including bone marrow aplasia. Black South African Fanconi anemia patients share a common causative founder mutation in the Fanconi G gene in 80% of cases (637_643delTACCGCC). The aim of this study was to investigate the genotype-physical phenotype correlation in a cohort of individuals homozygous for this mutation.Thirty-five black patients were recruited from tertiary level hematology/oncology clinics in South Africa. Participants were subjected to a comprehensive clinical examination, documenting growth, congenital anomalies, and phenotypic variability.Descriptive statistical analysis showed significant growth abnormalities in many patients and a high frequency (97%) of skin pigmentary anomalies. Subtle anomalies of the eyes, ears, and hands occurred frequently (≥70%). Apart from malformations of the kidney (in 37%) and gastrointestinal tract (in 8.5%), congenital anomalies of other systems including the cardiovascular and central nervous systems, genitalia, and vertebrae were infrequent (5%).The diagnosis of Fanconi anemia in black South African patients before the onset of hematological symptoms remains a clinical challenge, with the physical phenotype unlikely to be recognized by those without dysmorphology expertise.

Introduction Fanconi Anaemia (FA) is an autosomal recessive disorder characterized by defects in DNA repair associated with chromosomal instability and cellular hypersensitivity to DNA cross-linking agents such as mitomycin C (MMC). The clinical manifestation includes congenital and developmental abnormalities and bone marrow failure. FA also has a predisposition to cancer. Fifteen different genetic subtypes of FA have been described. In South Africa, with mixed ethnicity in the population, prevalence of FA ranges between is 1/22 000 for the white Afrikaners to 1/40 000 in the black South Africans. Evidence suggests that FA patients are chromosomally radiosensitive to ionising radiation but with very limited data. The aim of this study is to investigate chromosomal radiosensitivity and genomic instability of homozygous and heterozygous carriers of FA mutations compared to healthy individuals using the micronucleus (MN) assay. Materials and methods For the G0 MN assay, heparinised blood in culture medium was irradiated at 0 Gy (Baseline), 2 Gy and 4 Gy followed by the immediate stimulation of lymphocytes using phytohaemagglutinin (PHA). Cytochalasin B was added 23 hours later to inhibit cytoplasmic division. Cells were harvested 70 hours later. For the S/G2 MN assay, we used the same radiation doses but the culture was only irradiated 72 hours after addition of PHA. To detect DNA damage in the S/G2 phase of the cell cycle, the cells were harvested 8 hours post irradiation. The third assay is similar as the G0 MN assay except the cell damage is induced using MMC. All slides were stained with acridine orange and micronuclei were scored using a fluorescent microscope. Results The micronuclei frequencies are higher in the homozygous carriers compared to the heterozygous carriers and healthy individuals. Conclusions FA mutation carriers show higher chromosomal radiosensitivity and genomic instability compared to healthy individuals.

A comparative study of clinical, hematologic, and cytogenetic findings was made in 40 black and 35 white children with Fanconi anemia. The black children were Bantu-speaking Negroid stock of diverse tribal origin. The white children were predominantly Afrikaans stock of Dutch/German/French Huguenot origin. All of the patients had IFAR scores of 2 to 4+ and over 80% in each group had increased spontaneous and/or mutagen-induced chromosomal breakage (CB-positive). There were no significant clinical differences between black and white patients or between CB-pos and CB-neg patients, with the exception of white children in whom significantly more CB-pos patients had thumb and radial anomalies than the CB-neg patients. The age-at-onset of hematologic manifestations was the same for all groups, but more black than white CB-pos patients were severely anemic at the time of diagnosis. Response to androgen and steroid therapy occurred in only 33% of black children compared with 86-90% of white children; 81% of black patients died during the 18 year study period compared with 30% of white children, but the age at death was similar. More sophisticated studies are required to determine whether these differences are genetically determined or related to cultural, educational, and socio-economic differences between the two ethnic groups.

BACKGROUND IN ADULTS,: HIV increases the risk of certain cancers known, or thought, to have an underlying infectious etiology; the impact on the risk of cancer in children is less clear.Here, we report results of an on-going study at four pediatric oncology centers in South Africa in which children diagnosed with cancer are tested routinely for HIV. Odds ratios (OR) for the prevalence of various malignancies were calculated (with adjustment for age, sex, and center) for the children infected with HIV using all children with cancer and non-malignant conditions, but not infected with HIV, as a comparison group.Of 882 children with cancer, 38 were HIV infected (for 12 the HIV status was unknown). HIV was associated with Kaposi sarcoma (all 10 cases were HIV infected; P0.001) and with Burkitt lymphoma (OR = 46.2, 95% confidence interval (CI) 16.4-130.3; 13/33). For non-Burkitt non-Hodgkin lymphoma (NHL), 2/39 were HIV infected (OR = 5.0, 95% CI 0.9-27.0). No other cancer type was significantly associated with HIV, including lymphoid leukemias (OR = 0.4, 95% CI 0.04-2.9; 1/172).Only Kaposi sarcoma and Burkitt lymphoma were significantly associated with HIV infection although results for non-Burkitt NHL were suggestive. Notably, we did not identify an association between infection with HIV and lymphoid leukemias, for which an underlying infectious etiology has been suggested.

Two thirds of children with cancer never reach a specialist centre for treatment in South Africa. The majority of those who present have advanced disease. A campaign was undertaken to educate the public and the primary health workers on the Saint Siluan early warning signs of cancer in children. There was a statistically significant increase in the number of new patients referred in the 6 years following the campaign (P = 0.001), but did not succeed in achieving the referral of patients at earlier stages of disease. This list of the warning signs appears to be useful in promoting awareness of cancer.

Fine-needle aspiration biopsy (FNAB) has been widely accepted as a reliable diagnostic modality in the general pediatric population, but its role in pediatric oncology still remains elusive. With new treatment protocols subscribing to preoperative chemotherapy, the need for a quick, minimally invasive, and accurate diagnostic procedure has arisen. This study assesses the feasibility of FNAB in childhood malignancies to render a specific diagnosis on which treatment can be initiated. An 11-year retrospective study was done on FNABs in patients 19 years and under referred for clinically malignant mass lesions. Cases were confirmed with histology, immunocytochemistry, flow cytometry, or clinical follow-up. Of the 357 patients referred for FNABs, 36 patients were lost to follow-up and 31 FNABS were inadequate. A total of 290 cases were included in the study, of which 68 (23%) cases were benign and 222 (77%) were malignant. The most frequently occurring tumors were nephroblastoma (68), non-Hodgkin's lymphoma (39), rhabdomyosarcoma (22), Hodgkin's lymphoma (22), and neuroblastoma (22). The sensitivity of the procedure for neoplasia was 96.6%, the specificity 97.0%, positive predictive value 99.0%, and negative predictive value 90.1%, with a diagnostic accuracy of 96.7%. The ability of FNAB to enable a specific diagnosis to be made, that is correct and accurate subtyping of the tumor on which chemotherapy or radiotherapy could be commenced was 75.7%. This study shows that FNAB can be used with confidence to confirm malignancy in children. With clinicoradiological correlation and the aid of ancillary techniques, FNAB allows a rapid and accurate preoperative diagnosis for definitive therapy commencement in most cases.

A method for the measurement of 6-mercaptopurine (6MP) in urine using high-performance liquid chromatography is described. Urinary excretion of 6MP was measured in 46 children with acute lymphoblastic leukemia. The proportion of unchanged drug excreted after oral dosage in the morning was greater than after an evening dose (5.6 +/- 3.3% vs. 3.3 +/- 2.4%). Possible reasons for the discrepancy are discussed. In all children receiving 6MP in the morning, the drug was detected in urine at 2 and 4 h after ingestion. At 6 h, 6MP was still detectable in 77% of patients, at 8 h in 54%, at 10 h in 12%, and at 12 h in 8%. The reliability of urinary 6MP determination as a measure of drug compliance was assessed in 39 children accustomed to receiving their medication in the evening. 6MP was detected in 81% of first morning urine samples, indicating compliance with medication the preceding evening. The absence of 6MP in first morning urine samples did not necessarily indicate poor compliance because of the variability in 6MP excretion and unpredictable pattern of night voiding in children. The method was therefore a reliable measure of good short-term compliance. It also directed attention toward possible noncompliance in children with negative samples.