Challenge of pediatric oncology in Africa Hadley, Larry G.P., FRCS; Rouma, Bankole S., MD; Saad-Eldin, Yasser, MD
Seminars in pediatric surgery,
05/2012, Letnik:
21, Številka:
2
Journal Article
Recenzirano
The care of children with malignant solid tumors in sub-Saharan Africa is compromised by resource deficiencies that range from inadequate healthcare budgets and a paucity of appropriately trained ...personnel, to scarce laboratory facilities and inconsistent drug supplies. Patients face difficulties accessing healthcare, affording investigational and treatment protocols, and attending follow-up. Children routinely present with advanced local and metastatic disease and many children cannot be offered any effective treatment. Additionally, multiple comorbidities, including malaria, tuberculosis, and HIV when added to acute on chronic malnutrition, compound treatment-related toxicities. Survival rates are poor. Pediatric surgical oncology is not yet regarded as a health care priority by governments struggling to achieve their millennium goals. The patterns of childhood solid malignant tumors in Africa are discussed, and the difficulties encountered in their management are highlighted. Three pediatric surgeons from different regions of Africa reflect on their experiences and review the available literature. The overall incidence of pediatric solid malignant tumor is difficult to estimate in Africa because of lack of vital hospital statistics and national cancer registries in most of countries. The reported incidences vary between 5% and 15.5% of all malignant tumors. Throughout the continent, patterns of malignant disease vary with an obvious increase in the prevalence of Burkitt lymphoma (BL) and Kaposi sarcoma in response-increased prevalence of HIV disease. In northern Africa, the most common malignant tumor is leukemia, followed by brain tumors and nephroblastoma or neuroblastoma. In sub-Saharan countries, BL is the commonest tumor followed by nephroblastoma, non–Hodgkin lymphoma, and rhabdomyosarcoma. The overall 5-years survival varied between 5% (in Côte d'Ivoire before 2001) to 34% in Egypt and up to 70% in South Africa. In many reports, the survival rate of patients is not mentioned but is clearly very low in many sub-Saharan Africa countries (Sudan, Nigeria). Late presentation was observed for many tumors like nephroblastoma in Nigeria, 72% were stages III and IV or BL stages III and IV were observed in 40% and 30%, respectively. Africa bears a great burden of childhood cancer. Cancer is now curable in developed countries as survival rates approach 80%, but in Africa, >80% of children still die without access to adequate treatment. Sharpening the needlepoint of surgical expertise will, of itself, not compensate for the major infrastructural deficiencies, but must proceed in tandem with resource development and allow heath planners to realize that pediatric surgical oncology is a cost-effective service that can uplift regional services.
The incidence of invasive aspergillosis was estimated among 4621 hematopoietic stem cell transplants (HSCT) and 4110 solid organ transplants (SOT) at 19 sites dispersed throughout the United States, ...during a 22 month period from 1 March 2001 through 31 December 2002. Cases were identified using the consensus definitions for proven and probable infection developed by the Invasive Fungal Infections Cooperative Group of the European Organization for Research and Treatment of Cancer and the Mycoses Study Group of the National Institute of Allergy and Infectious Diseases. The cumulative incidence (CI) of aspergillosis was calculated for the first episode of the infection that occurred within the specified time period after transplantation. To obtain an aggregate CI for each type of transplant, data from participating sites were weighted according to the proportion of transplants followed-up for specified time periods (four and 12 months for HSCT; six and 12 months for SOT). The aggregate CI of aspergillosis at 12 months was 0.5% after autologous HSCT, 2.3% after allogeneic HSCT from an HLA-matched related donor, 3.2% after transplantation from an HLA-mismatched related donor, and 3.9% after transplantation from an unrelated donor. The aggregate CI at 12 months was similar following myeloablative or non-myeloablative conditioning before allogeneic HSCT (3.1 vs. 3.3%). After HSCT, mortality at 3 months following diagnosis of aspergillosis ranged from 53.8% of autologous transplants to 84.6% of unrelated-donor transplants. The aggregate CI of aspergillosis at 12 months was 2.4% after lung transplantation, 0.8% after heart transplantation, 0.3% after liver transplantation, and 0.1% after kidney transplantation. After SOT, mortality at three months after diagnosis of aspergillosis ranged from 20% for lung transplants to 66.7% for heart and kidney transplants. The Aspergillus spp. associated with infections after HSCT included A. fumigatus (56%), A. flavus (18.7%), A. terreus (16%), A. niger (8%), and A. versicolor (1.3%). Those associated with infections after SOT included A. fumigatus (76.4%), A. flavus (11.8%), and A. terreus (11.8%). In conclusion, we found that invasive aspergillosis is an uncommon complication of HSCT and SOT, but one that continues to be associated with poor outcomes. Our CI figures are lower compared to those of previous reports. The reasons for this are unclear, but may be related to changes in transplantation practices, diagnostic methods, and supportive care.
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.
Neuroblastoma is uncommon in Africa, but when seen usually presents as high-risk disease with a poor prognosis. This aggressive biology of the tumour is frequently augmented by delayed presentation. ...Current treatment depends upon technologies and skills that are scarce in developing countries and the cost involved is generally beyond the means of healthcare providers who are faced with a myriad more pressing healthcare issues. The presentation, treatment and outcome of 45 African children with neuroblastoma are described. Due to a lack of resources precise risk stratification was impossible but visceral or bone metastases were present in 73% of patients at diagnosis. In 91% the primary tumour was intra-abdominal. Three children (7%) were paraplegic on admission. A localised tumour was seen in one child (2%). Fifteen children (33%) underwent a surgical procedure, with intent to cure in five among whom resection was incomplete in three. For all other children, treatment was palliative using chemotherapy with judicious use of radiotherapy. Thirteen children (29%) survived longer than six months. Overall survival at three years was 4%.
Background: Assessment of nutritional status of paediatric oncology patients is crucial, as it may influence treatment and clinical outcomes. Concurrent malnutrition and cancer in children may lead ...to reduced chemotherapy delivery due to impaired tolerance and increased toxicity.
Aim: This study aimed to determine the relationship between nutritional status and the prevalence, frequency and duration of treatment-related neutropenia in a cohort of South African children with nephroblastoma.
Methods: Seventy-seven children between the ages of 1 and 12 years diagnosed with nephroblastoma at Inkosi Albert Luthuli Central Hospital (IALCH), Durban, between 2004 and 2012, were studied prospectively. Nutritional status was assessed using weight, height, mid-upper arm circumference (MUAC), triceps skinfold thickness (TSFT) and serum albumin. The administration of filgastrim (Neupogen®) was used as a surrogate for neutropenia and the frequency and duration of its use was recorded.
Results: There was a significant relationship between the prevalence of treatment-induced neutropenia and malnutrition defined by MUAC. The mean frequency and duration of neutropenia was significantly higher in those classified as malnourished using MUAC. There was a positive correlation between frequency and duration of neutropenia.
Conclusions: Malnutrition was prevalent among children with nephroblastoma. The prevalence of treatment-induced neutropenia was higher in those with poor nutritional status, identified by MUAC. Poor nutritional status according to MUAC was also linked to an increased frequency and duration of neutropenia. It is important to include MUAC in the nutritional assessment of children with nephroblastoma.
Background
In developing countries up to 77% of children with cancer have been shown to be malnourished on admission. High rates of malnutrition occur due to factors such as poverty and advanced ...disease. Weight can be an inaccurate parameter for nutritional assessment of children with solid tumours as it is influenced by tumour mass. This study aimed to assess the prevalence of malnutrition amongst children with Wilms tumour (WT), the level of nutritional support received on admission and the influence of nutritional status on outcome.
Methods
Seventy‐six children diagnosed with WT and admitted to Inkosi Albert Luthuli Central Hospital between 2004 and 2012 were studied prospectively. Nutritional assessment was conducted using weight, height, mid‐upper arm circumference (MUAC) and triceps skinfold thickness (TSFT) prior to initiating treatment. Outcome was determined 2 years after admission. Time until commencement of nutritional resuscitation and nature, thereof, were recorded.
Results
Stunting and wasting was evident in 12% and 15% of patients, respectively. The prevalence of malnutrition was 66% when MUAC, TSFT and albumin were used. Malnutrition was not a predictor of poor outcome and did not predict advanced disease. The majority of patients (84%) received nutritional resuscitation within 2 weeks of admission.
Conclusions
When classifying nutritional status in children with WT, the utilisation of weight and height in isolation can lead to an underestimation of the prevalence of malnutrition. Nutritional assessment of children with WT should also include MUAC and TSFT. Early aggressive nutritional resuscitation is recommended.
Paediatric surgical disease is a neglected health problem. Patients travel great distances to tertiary level care for management. This study aimed at analysing referral patterns to design an outreach ...programme for paediatric surgery in KwaZulu Natal. Data forms of patients referred to the service between January and July 2016 were correlated with the clinical record. Delays in management were compared to morbidity and mortality. Out of 781, 158 referrals were accepted as emergencies. The majority (62%) were children aged < 1 year. Gastro-intestinal problems (38.4%) and congenital anomalies (26.9%) formed the majority. Patients who died had a significantly longer delay in transfer. Longer total delay was associated with statistically significant greater morbidity. In a setting where a large rural population is served by single-centre tertiary care, delays exist and contribute to morbidity. The authors advocate the establishment of an outreach programme to address these issues.
Abstract Peritonitis is a progressive disease leading inexorably from local peritoneal irritation to overwhelming sepsis and death unless this trajectory is interrupted by timely and effective ...therapy. In children peritonitis is usually secondary to intraperitoneal disease, the nature of which varies around the world. In rich countries, appendicitis is the principal cause whilst in poor countries diseases such as typhoid must be considered in the differential diagnosis. Where resources are limited, the clinical diagnosis of peritonitis mandates laparotomy for diagnosis and source control. In regions with unlimited resources, radiological investigation, ultrasound, CT scan or MRI may be used to select patients for non-operative management. For patients with appendicitis, laparoscopic surgery has achieved results comparable to open operation; however, in many centres open operation remains the standard. In complicated peritonitis “damage control surgery” may be appropriate wherein source control is undertaken as an emergency with definitive repair or reconstruction awaiting improvement in the patient׳s general condition. Awareness of abdominal compartment syndrome is essential. Primary peritonitis in rich countries is seen in high-risk groups, such as steroid-dependent nephrotic syndrome patients, whilst in poor countries the at-risk population is less well defined and the diagnosis is often made at surgery.
Background
Outcome data for neuroblastoma in sub‐Saharan Africa are minimal, whereas poor outcome is reported in low‐ and middle‐income countries. A multi‐institutional retrospective study across ...South Africa was undertaken to determine outcome.
Methods
Patients treated between January 2000 and December 2014 in nine South African pediatric oncology units were included. Kaplan–Meier curves and Cox regression models were employed to determine two‐year survival rates and to identify prognostic factors.
Results
Data from 390 patients were analyzed. The median age was 39.9 months (range, 0–201 months). The majority presented with stage 4 disease (70%). The main chemotherapy regimens were OPEC/OJEC (44.8%), St Jude NB84 protocol (28.96%), and Rapid COJEC (22.17%). Only 44.4% had surgery across all risk groups, whereas only 16.5% of high‐risk patients received radiotherapy. The two‐year overall survival (OS) for the whole cohort was 37.6%: 94.1%, 81.6%, and 66.7%, respectively, for the very‐low‐risk, low‐risk, and intermediate‐risk groups and 27.6% for the high‐risk group (P < 0.001, 95% CI). The median survival time for the whole group was 13 months (mean, 41.9 months; range, 0.1–209 months). MYCN‐nonamplified patients had a superior two‐year OS of 51.3% in comparison with MYCN‐amplified patients at 37.3% (P = 0.002, 95% CI).
Conclusions
Limited disease had an OS comparable with high‐income countries, but advanced disease had a poor OS. South Africa should focus on early diagnosis and implementation of a national protocol with equitable access to treatment.